Brentuximab Vedotin og Nivolumab med eller uten Ipilimumab ved behandling av pasienter med residiverende eller refraktær Hodgkin-lymfom
En fase I-studie med en ekspansjonskohort/randomisert fase II-studie av kombinasjoner av Ipilimumab, Nivolumab og Brentuximab Vedotin hos pasienter med residiverende/refraktær Hodgkin-lymfom
This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.
Studieoversikt
Status
Detaljert beskrivelse
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the complete response (CR) rate for the regimens of brentuximab vedotin and nivolumab compared to brentuximab vedotin, ipilimumab, and nivolumab. (Phase II; adult cohort [aged >= 18 years]) III. To characterize the safety and toxicity of treatment combination in the pediatric population. (Phase II; pediatric cohort [aged 12-17 years])
SECONDARY OBJECTIVES:
I. To evaluate complete response (CR) rate, partial response (PR) rate and overall response rate (ORR), for the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the duration of remission (DOR) to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase I) III. To evaluate the progression-free survival (PFS) and the overall survival (OS) in patients receiving the combination of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) IV. To evaluate the ORR, PR, and stable disease (SD) rate for the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) V. To evaluate the DOR to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase II) VI. To evaluate the 5 year PFS and OS in patients receiving the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) VII. To further evaluate the safety and characterize the toxicity for the combinations of brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II)
CORRELATIVE STUDY OBJECTIVES:
I. To evaluate the ability of these combinations to alter tumor specific T cell immunity. (Phase I) II. To evaluate the effects of these combinations on systemic immunity. (Phase I) III. To evaluate a panel of cytokine and T cell specific biomarkers from the peripheral blood as a potential immune signature of treatment response to therapy with these combinations for patients with relapsed/refractory Hodgkin lymphoma (HL). (Phase I) IV. To evaluate using gene expression profiling (GEP) a signature of response to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase I) V. To evaluate the ability of these combinations to alter tumor specific T cell immunity, and circulating T cell phenotypes, in patients as a function of treatment response at multiple timepoints during therapy. (Phase II) VI. To evaluate peripheral blood cytokine profiles in responding and resistant patients at multiple timepoints during therapy. (Phase II) VII. To evaluate using GEP a signature of response versus (vs.) resistance to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase II) VIII. To evaluate the influence of human gut microbiome dysbiosis on HL lymphomagenesis and the systemic immune response. (Phase II)
IMAGING CORRELATIVE STUDY OBJECTIVES:
I. To evaluate atypical response patterns with currently available response evaluation criteria. (Phase II) II. To correlate response evaluated using currently available response evaluation criteria with duration of response (PFS, event free survival [EFS], failure free survival [FFS]). (Phase II) III. To evaluate response patterns in different immunotherapy treatment schemes and correlate with historical data using chemotherapy. (Phase II) IV. To correlate imaging changes in all treatment schemes quantitatively with PFS. (Phase II)
EXPLORATORY OBJECTIVES:
I. Evaluate outcomes (CR, PFS) between patients with/without prior transplants. (Phase II) II. Evaluate outcomes (PFS, OS) between the patients who stay on treatment and do not go to transplant in both arms (the post auto and the few others who don't want transplant) vs the patients who go off for transplant. (Phase II) III. Evaluate outcomes (CR, PFS) in pediatric population (age 12 to < 18 years of age) vs. adult population. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin, ipilimumab, and nivolumab followed by a phase II study.
PHASE I: Patients are assigned into 1 of 3 arms.
ARM I: Patients receive brentuximab vedotin intravenously (IV) over 90 minutes on day 1 of cycles 1-16 and ipilimumab IV over 30 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and nivolumab IV over 90 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.
All patients also undergo computed tomography (CT) or positron emission tomography (PET) scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
After completion of phase I study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 2 years. After completion of phase II study treatment, patients are followed up for 10 years.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
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Alabama
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Birmingham, Alabama, Forente stater, 35233
- University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, Forente stater, 35233
- Children's Hospital of Alabama
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Alaska
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Anchorage, Alaska, Forente stater, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Forente stater, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Forente stater, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Forente stater, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Forente stater, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Forente stater, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Forente stater, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Forente stater, 99504
- Anchorage Radiation Therapy Center
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Fairbanks, Alaska, Forente stater, 99701
- Fairbanks Memorial Hospital
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Arizona
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Kingman, Arizona, Forente stater, 86401
- Kingman Regional Medical Center
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Phoenix, Arizona, Forente stater, 85004
- Cancer Center at Saint Joseph's
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Arkansas
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Fort Smith, Arkansas, Forente stater, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, Forente stater, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Antioch, California, Forente stater, 94531
- Kaiser Permanente-Deer Valley Medical Center
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Arroyo Grande, California, Forente stater, 93420
- PCR Oncology
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Arroyo Grande, California, Forente stater, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, Forente stater, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Dublin, California, Forente stater, 94568
- Kaiser Permanente Dublin
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Fremont, California, Forente stater, 94538
- Kaiser Permanente-Fremont
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Fresno, California, Forente stater, 93720
- Kaiser Permanente-Fresno
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Fresno, California, Forente stater, 93720
- Fresno Cancer Center
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Modesto, California, Forente stater, 95356
- Kaiser Permanente-Modesto
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Oakland, California, Forente stater, 94611
- Kaiser Permanente-Oakland
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Oakland, California, Forente stater, 94611
- Kaiser Permanente Oakland-Broadway
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Orange, California, Forente stater, 92868
- Children's Hospital of Orange County
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Palo Alto, California, Forente stater, 94304
- Stanford Cancer Institute Palo Alto
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Rancho Cordova, California, Forente stater, 95670
- Kaiser Permanente-Rancho Cordova Cancer Center
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Redwood City, California, Forente stater, 94063
- Kaiser Permanente-Redwood City
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Richmond, California, Forente stater, 94801
- Kaiser Permanente-Richmond
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Rohnert Park, California, Forente stater, 94928
- Rohnert Park Cancer Center
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Roseville, California, Forente stater, 95678
- The Permanente Medical Group-Roseville Radiation Oncology
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Roseville, California, Forente stater, 95661
- Kaiser Permanente-Roseville
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Sacramento, California, Forente stater, 95814
- Kaiser Permanente Downtown Commons
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Sacramento, California, Forente stater, 95823
- Kaiser Permanente-South Sacramento
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Sacramento, California, Forente stater, 95823
- South Sacramento Cancer Center
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Sacramento, California, Forente stater, 95825
- Kaiser Permanente Sacramento Medical Center
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San Francisco, California, Forente stater, 94115
- Kaiser Permanente-San Francisco
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San Francisco, California, Forente stater, 94158
- UCSF Medical Center-Mission Bay
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San Jose, California, Forente stater, 95119
- Kaiser Permanente-Santa Teresa-San Jose
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San Leandro, California, Forente stater, 94577
- Kaiser Permanente San Leandro
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San Luis Obispo, California, Forente stater, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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San Rafael, California, Forente stater, 94903
- Kaiser San Rafael-Gallinas
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San Rafael, California, Forente stater, 94903
- Kaiser Permanente-San Rafael
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Santa Clara, California, Forente stater, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Maria, California, Forente stater, 93444
- Mission Hope Medical Oncology - Santa Maria
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Santa Rosa, California, Forente stater, 95403
- Kaiser Permanente-Santa Rosa
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South San Francisco, California, Forente stater, 94080
- Kaiser Permanente Cancer Treatment Center
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South San Francisco, California, Forente stater, 94080
- Kaiser Permanente-South San Francisco
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Stockton, California, Forente stater, 95210
- Kaiser Permanente-Stockton
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Vacaville, California, Forente stater, 95688
- Kaiser Permanente Medical Center-Vacaville
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Vallejo, California, Forente stater, 94589
- Kaiser Permanente-Vallejo
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Walnut Creek, California, Forente stater, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Forente stater, 80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora, Colorado, Forente stater, 80012
- The Medical Center of Aurora
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Boulder, Colorado, Forente stater, 80303
- Boulder Community Foothills Hospital
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Boulder, Colorado, Forente stater, 80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial, Colorado, Forente stater, 80112
- Rocky Mountain Cancer Centers - Centennial
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Colorado Springs, Colorado, Forente stater, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, Forente stater, 80907
- Rocky Mountain Cancer Centers-Penrose
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Denver, Colorado, Forente stater, 80218
- Presbyterian - Saint Lukes Medical Center - Health One
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Denver, Colorado, Forente stater, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Denver, Colorado, Forente stater, 80220
- Rose Medical Center
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Denver, Colorado, Forente stater, 80218
- Rocky Mountain Cancer Centers-Midtown
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Denver, Colorado, Forente stater, 80220
- Rocky Mountain Cancer Centers-Rose
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Denver, Colorado, Forente stater, 80204
- Denver Health Medical Center
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Denver, Colorado, Forente stater, 80218
- Colorado Blood Cancer Institute
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Denver, Colorado, Forente stater, 80204
- Cancer Center of Colorado at Sloan's Lake
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Denver, Colorado, Forente stater, 80209
- The Women's Imaging Center
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Denver, Colorado, Forente stater, 80206
- National Jewish Health-Main Campus
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Denver, Colorado, Forente stater, 80220
- Western Surgical Care
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Denver, Colorado, Forente stater, 80218
- Saint Joseph Hospital - Cancer Centers of Colorado
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Denver, Colorado, Forente stater, 80210
- AdventHealth Porter
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Durango, Colorado, Forente stater, 81301
- Mercy Medical Center
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Durango, Colorado, Forente stater, 81301
- CommonSpirit Cancer Center Mercy
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Englewood, Colorado, Forente stater, 80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood, Colorado, Forente stater, 80113
- Swedish Medical Center
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Englewood, Colorado, Forente stater, 80113
- Rocky Mountain Cancer Centers - Swedish
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Golden, Colorado, Forente stater, 80401
- Mountain Blue Cancer Care Center
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Golden, Colorado, Forente stater, 80401
- National Jewish Health-Western Hematology Oncology
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Grand Junction, Colorado, Forente stater, 81501
- Saint Mary's Hospital and Regional Medical Center
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Greeley, Colorado, Forente stater, 80631
- Banner North Colorado Medical Center
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Lafayette, Colorado, Forente stater, 80026
- Good Samaritan Hospital - Cancer Centers of Colorado
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Lakewood, Colorado, Forente stater, 80228
- Rocky Mountain Cancer Centers-Lakewood
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Lakewood, Colorado, Forente stater, 80228
- CommonSpirit Saint Anthony Hospital Cancer Center
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Littleton, Colorado, Forente stater, 80120
- Rocky Mountain Cancer Centers-Littleton
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Littleton, Colorado, Forente stater, 80122
- AdventHealth Littleton
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Lone Tree, Colorado, Forente stater, 80124
- Sky Ridge Medical Center
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Lone Tree, Colorado, Forente stater, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
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Longmont, Colorado, Forente stater, 80501
- Longmont United Hospital
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Longmont, Colorado, Forente stater, 80501
- Rocky Mountain Cancer Centers-Longmont
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Loveland, Colorado, Forente stater, 80539
- Banner North Colorado Medical Center - Loveland Campus
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Parker, Colorado, Forente stater, 80138
- Rocky Mountain Cancer Centers-Parker
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Parker, Colorado, Forente stater, 80138
- AdventHealth Parker
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Pueblo, Colorado, Forente stater, 81008
- Rocky Mountain Cancer Centers - Pueblo
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Thornton, Colorado, Forente stater, 80260
- Rocky Mountain Cancer Centers-Thornton
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Thornton, Colorado, Forente stater, 80260
- National Jewish Health-Northern Hematology Oncology
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Wheat Ridge, Colorado, Forente stater, 80401
- Intermountain Health Lutheran Hospital
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District of Columbia
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Washington D.C., District of Columbia, Forente stater, 20010
- Children's National Medical Center
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Florida
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Fort Myers, Florida, Forente stater, 33905
- Regional Cancer Center-Lee Memorial Health System
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Fort Myers, Florida, Forente stater, 33908
- Golisano Children's Hospital of Southwest Florida
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St. Petersburg, Florida, Forente stater, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, Forente stater, 33606
- Tampa General Hospital
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Tampa, Florida, Forente stater, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Emory University Hospital/Winship Cancer Institute
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Atlanta, Georgia, Forente stater, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
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Hawaii
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Honolulu, Hawaii, Forente stater, 96819
- Kaiser Permanente Moanalua Medical Center
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Idaho
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Boise, Idaho, Forente stater, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, Forente stater, 83712
- Saint Luke's Cancer Institute - Boise
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Caldwell, Idaho, Forente stater, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Forente stater, 83814
- Kootenai Health - Coeur d'Alene
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Emmett, Idaho, Forente stater, 83617
- Walter Knox Memorial Hospital
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Fruitland, Idaho, Forente stater, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Forente stater, 83642
- Idaho Urologic Institute-Meridian
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Meridian, Idaho, Forente stater, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Forente stater, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Nampa, Idaho, Forente stater, 83687
- Saint Luke's Cancer Institute - Nampa
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Post Falls, Idaho, Forente stater, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Forente stater, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Twin Falls, Idaho, Forente stater, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, Forente stater, 62002
- OSF Saint Anthony's Health Center
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Aurora, Illinois, Forente stater, 60504
- Rush-Copley Medical Center
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Bloomington, Illinois, Forente stater, 61704
- Illinois CancerCare-Bloomington
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Canton, Illinois, Forente stater, 61520
- Illinois CancerCare-Canton
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Carbondale, Illinois, Forente stater, 62902
- Memorial Hospital of Carbondale
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Carterville, Illinois, Forente stater, 62918
- SIH Cancer Institute
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Carthage, Illinois, Forente stater, 62321
- Illinois CancerCare-Carthage
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Centralia, Illinois, Forente stater, 62801
- Centralia Oncology Clinic
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Chicago, Illinois, Forente stater, 60611
- Northwestern University
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Chicago, Illinois, Forente stater, 60612
- University of Illinois
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Chicago, Illinois, Forente stater, 60612
- Rush MD Anderson Cancer Center
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Danville, Illinois, Forente stater, 61832
- Carle at The Riverfront
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Decatur, Illinois, Forente stater, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Forente stater, 62526
- Cancer Care Specialists of Illinois - Decatur
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Dixon, Illinois, Forente stater, 61021
- Illinois CancerCare-Dixon
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Effingham, Illinois, Forente stater, 62401
- Crossroads Cancer Center
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Effingham, Illinois, Forente stater, 62401
- Carle Physician Group-Effingham
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Eureka, Illinois, Forente stater, 61530
- Illinois CancerCare-Eureka
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Galesburg, Illinois, Forente stater, 61401
- Western Illinois Cancer Treatment Center
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Galesburg, Illinois, Forente stater, 61401
- Illinois CancerCare-Galesburg
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Joliet, Illinois, Forente stater, 60435
- Duly Health and Care Joliet
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Kewanee, Illinois, Forente stater, 61443
- Illinois CancerCare-Kewanee Clinic
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Macomb, Illinois, Forente stater, 61455
- Illinois CancerCare-Macomb
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Mattoon, Illinois, Forente stater, 61938
- Carle Physician Group-Mattoon/Charleston
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Mount Vernon, Illinois, Forente stater, 62864
- SSM Health Good Samaritan
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O'Fallon, Illinois, Forente stater, 62269
- Cancer Care Center of O'Fallon
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Ottawa, Illinois, Forente stater, 61350
- Illinois CancerCare-Ottawa Clinic
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Pekin, Illinois, Forente stater, 61554
- Illinois CancerCare-Pekin
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Peoria, Illinois, Forente stater, 61636
- Methodist Medical Center of Illinois
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Peoria, Illinois, Forente stater, 61615
- Illinois CancerCare-Peoria
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Peru, Illinois, Forente stater, 61354
- Illinois CancerCare-Peru
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Peru, Illinois, Forente stater, 61354
- Valley Radiation Oncology
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Princeton, Illinois, Forente stater, 61356
- Illinois CancerCare-Princeton
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Springfield, Illinois, Forente stater, 62702
- Southern Illinois University School of Medicine
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Springfield, Illinois, Forente stater, 62702
- Springfield Clinic
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Springfield, Illinois, Forente stater, 62781
- Springfield Memorial Hospital
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Swansea, Illinois, Forente stater, 62226
- Southwest Illinois Health Services LLP
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Urbana, Illinois, Forente stater, 61801
- Carle Cancer Center
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Urbana, Illinois, Forente stater, 61801
- The Carle Foundation Hospital
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Washington, Illinois, Forente stater, 61571
- Illinois CancerCare - Washington
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Yorkville, Illinois, Forente stater, 60560
- Rush-Copley Healthcare Center
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Indiana
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Evansville, Indiana, Forente stater, 47713
- Deaconess Clinic Downtown
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Indianapolis, Indiana, Forente stater, 46202
- Indiana University/Melvin and Bren Simon Cancer Center
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Newburgh, Indiana, Forente stater, 47630
- Chancellor Center for Oncology
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Iowa
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Clive, Iowa, Forente stater, 50325
- Mercy Cancer Center-West Lakes
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Clive, Iowa, Forente stater, 50325
- UI Health Care Mission Cancer and Blood - West Des Moines Clinic
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Council Bluffs, Iowa, Forente stater, 51503
- Alegent Health Mercy Hospital
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Creston, Iowa, Forente stater, 50801
- Greater Regional Medical Center
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Des Moines, Iowa, Forente stater, 50314
- Mercy Medical Center - Des Moines
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Des Moines, Iowa, Forente stater, 50314
- UI Health Care Mission Cancer and Blood - Laurel Clinic
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West Des Moines, Iowa, Forente stater, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, Forente stater, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, Forente stater, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, Forente stater, 40004
- CommonSpirit Saint Joseph Hospital - Bardstown
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Corbin, Kentucky, Forente stater, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, Forente stater, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, Forente stater, 40509
- CommonSpirit Saint Joseph Medical Center - East Lexington
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London, Kentucky, Forente stater, 40741
- CommonSpirit Saint Joseph Hospital London
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Louisville, Kentucky, Forente stater, 40202
- Jewish Hospital
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Louisville, Kentucky, Forente stater, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, Forente stater, 40215
- Saints Mary and Elizabeth Hospital
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Paducah, Kentucky, Forente stater, 42003
- Mercy Health - Paducah Cancer Center
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Shepherdsville, Kentucky, Forente stater, 40165
- Jewish Hospital Medical Center South
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Louisiana
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Baton Rouge, Louisiana, Forente stater, 70805
- LSU Health Baton Rouge-North Clinic
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Baton Rouge, Louisiana, Forente stater, 70809
- Louisiana Hematology Oncology Associates LLC
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Baton Rouge, Louisiana, Forente stater, 70809
- Mary Bird Perkins Cancer Center
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Baton Rouge, Louisiana, Forente stater, 70808
- Our Lady of The Lake
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Baton Rouge, Louisiana, Forente stater, 70808
- Our Lady of the Lake Physician Group
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Covington, Louisiana, Forente stater, 70433
- Northshore Oncology Associates-Covington
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Houma, Louisiana, Forente stater, 70360
- Terrebonne General Medical Center
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Houma, Louisiana, Forente stater, 70360
- Oncology Center of The South Incorporated
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Maryland
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Baltimore, Maryland, Forente stater, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, Forente stater, 21229
- Saint Agnes Hospital
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Bethesda, Maryland, Forente stater, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, Forente stater, 02111
- Tufts Medical Center
-
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Michigan
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Port Huron, Michigan, Forente stater, 48060
- Lake Huron Medical Center
-
Port Huron, Michigan, Forente stater, 48060
- Huron Medical Center PC
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Minnesota
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Aitkin, Minnesota, Forente stater, 56431
- Riverwood Healthcare Center
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Brainerd, Minnesota, Forente stater, 56401
- Essentia Health Saint Joseph's Medical Center
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Deer River, Minnesota, Forente stater, 56636
- Essentia Health - Deer River Clinic
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Detroit Lakes, Minnesota, Forente stater, 56501
- Essentia Health Saint Mary's - Detroit Lakes Clinic
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Duluth, Minnesota, Forente stater, 55805
- Essentia Health Cancer Center
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Duluth, Minnesota, Forente stater, 55805
- Essentia Health Saint Mary's Medical Center
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Duluth, Minnesota, Forente stater, 55805
- Miller-Dwan Hospital
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Fergus Falls, Minnesota, Forente stater, 56537
- Lake Region Healthcare Corporation-Cancer Care
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Fosston, Minnesota, Forente stater, 56542
- Essentia Health - Fosston
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Hibbing, Minnesota, Forente stater, 55746
- Essentia Health Hibbing Clinic
-
Park Rapids, Minnesota, Forente stater, 56470
- Essentia Health - Park Rapids
-
Rochester, Minnesota, Forente stater, 55905
- Mayo Clinic in Rochester
-
Sandstone, Minnesota, Forente stater, 55072
- Essentia Health Sandstone
-
Virginia, Minnesota, Forente stater, 55792
- Essentia Health Virginia Clinic
-
-
Missouri
-
Ballwin, Missouri, Forente stater, 63011
- Mercy Oncology and Hematology - Clayton-Clarkson
-
Bolivar, Missouri, Forente stater, 65613
- Central Care Cancer Center - Bolivar
-
Bonne Terre, Missouri, Forente stater, 63628
- Parkland Health Center-Bonne Terre
-
Branson, Missouri, Forente stater, 65616
- Cox Cancer Center Branson
-
Cape Girardeau, Missouri, Forente stater, 63703
- Saint Francis Medical Center
-
Cape Girardeau, Missouri, Forente stater, 63703
- Mercy Cancer Center - Cape Girardeau
-
Chesterfield, Missouri, Forente stater, 63017
- Saint Luke's Hospital
-
City of Saint Peters, Missouri, Forente stater, 63376
- Siteman Cancer Center at Saint Peters Hospital
-
Creve Coeur, Missouri, Forente stater, 63141
- Siteman Cancer Center at West County Hospital
-
Farmington, Missouri, Forente stater, 63640
- Parkland Health Center - Farmington
-
Jefferson City, Missouri, Forente stater, 65109
- MU Health Care Goldschmidt Cancer Center
-
Joplin, Missouri, Forente stater, 64804
- Freeman Health System
-
Joplin, Missouri, Forente stater, 64804
- Mercy Hospital Joplin
-
Kansas City, Missouri, Forente stater, 64108
- Children's Mercy Hospitals and Clinics
-
Rolla, Missouri, Forente stater, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
-
Rolla, Missouri, Forente stater, 65401
- Phelps Health Delbert Day Cancer Institute
-
Saint Joseph, Missouri, Forente stater, 64506
- Heartland Regional Medical Center
-
Sainte Genevieve, Missouri, Forente stater, 63670
- Sainte Genevieve County Memorial Hospital
-
Springfield, Missouri, Forente stater, 65807
- CoxHealth South Hospital
-
Springfield, Missouri, Forente stater, 65804
- Mercy Hospital Springfield
-
St Louis, Missouri, Forente stater, 63110
- Washington University School of Medicine
-
St Louis, Missouri, Forente stater, 63129
- Siteman Cancer Center-South County
-
St Louis, Missouri, Forente stater, 63136
- Siteman Cancer Center at Christian Hospital
-
St Louis, Missouri, Forente stater, 63131
- Missouri Baptist Medical Center
-
St Louis, Missouri, Forente stater, 63109
- Mercy Infusion Center - Chippewa
-
St Louis, Missouri, Forente stater, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, Forente stater, 63128
- Mercy Hospital South
-
Sullivan, Missouri, Forente stater, 63080
- Missouri Baptist Sullivan Hospital
-
Washington, Missouri, Forente stater, 63090
- Mercy Hospital Washington
-
-
Montana
-
Anaconda, Montana, Forente stater, 59711
- Community Hospital of Anaconda
-
Billings, Montana, Forente stater, 59101
- Billings Clinic Cancer Center
-
Billings, Montana, Forente stater, 59101
- Saint Vincent Healthcare
-
Billings, Montana, Forente stater, 59102
- Saint Vincent Frontier Cancer Center
-
Bozeman, Montana, Forente stater, 59715
- Bozeman Health Deaconess Hospital
-
Butte, Montana, Forente stater, 59701
- Saint James Community Hospital and Cancer Treatment Center
-
Great Falls, Montana, Forente stater, 59405
- Great Falls Clinic
-
Great Falls, Montana, Forente stater, 59405
- Benefis Sletten Cancer Institute
-
Helena, Montana, Forente stater, 59601
- Saint Peter's Community Hospital
-
Kalispell, Montana, Forente stater, 59901
- Logan Health Medical Center
-
Missoula, Montana, Forente stater, 59802
- Saint Patrick Hospital - Community Hospital
-
Missoula, Montana, Forente stater, 59804
- Community Medical Center
-
-
Nebraska
-
Grand Island, Nebraska, Forente stater, 68803
- Nebraska Cancer Specialists/Oncology Hematology West PC
-
Kearney, Nebraska, Forente stater, 68847
- CHI Health Good Samaritan
-
Kearney, Nebraska, Forente stater, 68845
- Fred and Pamela Buffett Cancer Center - Kearney
-
Lincoln, Nebraska, Forente stater, 68510
- Saint Elizabeth Regional Medical Center
-
Omaha, Nebraska, Forente stater, 68124
- Alegent Health Bergan Mercy Medical Center
-
Omaha, Nebraska, Forente stater, 68122
- Alegent Health Immanuel Medical Center
-
Omaha, Nebraska, Forente stater, 68130
- Alegent Health Lakeside Hospital
-
Omaha, Nebraska, Forente stater, 68122
- Hematology and Oncology Consultants PC
-
Papillion, Nebraska, Forente stater, 68046
- Midlands Community Hospital
-
-
Nevada
-
Carson City, Nevada, Forente stater, 89703
- Carson Tahoe Regional Medical Center
-
Henderson, Nevada, Forente stater, 89052
- Comprehensive Cancer Centers of Nevada - Henderson
-
Henderson, Nevada, Forente stater, 89052
- Cancer and Blood Specialists-Henderson
-
Henderson, Nevada, Forente stater, 89052
- Las Vegas Cancer Center-Henderson
-
Henderson, Nevada, Forente stater, 89074
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
-
Henderson, Nevada, Forente stater, 89052
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
-
Henderson, Nevada, Forente stater, 89074
- Las Vegas Urology - Green Valley
-
Henderson, Nevada, Forente stater, 89074
- Las Vegas Urology - Pebble
-
Henderson, Nevada, Forente stater, 89074
- Urology Specialists of Nevada - Green Valley
-
Henderson, Nevada, Forente stater, 89074
- Oncology Las Vegas - Henderson
-
Las Vegas, Nevada, Forente stater, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, Forente stater, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, Forente stater, 89102
- OptumCare Cancer Care at Charleston
-
Las Vegas, Nevada, Forente stater, 89106
- Radiation Oncology Centers of Nevada Central
-
Las Vegas, Nevada, Forente stater, 89119
- Radiation Oncology Centers of Nevada Southeast
-
Las Vegas, Nevada, Forente stater, 89128
- Comprehensive Cancer Centers of Nevada - Northwest
-
Las Vegas, Nevada, Forente stater, 89128
- OptumCare Cancer Care at MountainView
-
Las Vegas, Nevada, Forente stater, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, Forente stater, 89144
- Comprehensive Cancer Centers of Nevada - Town Center
-
Las Vegas, Nevada, Forente stater, 89144
- Comprehensive Cancer Centers of Nevada-Summerlin
-
Las Vegas, Nevada, Forente stater, 89148
- Comprehensive Cancer Centers of Nevada
-
Las Vegas, Nevada, Forente stater, 89169
- Comprehensive Cancer Centers of Nevada - Central Valley
-
Las Vegas, Nevada, Forente stater, 89102
- University Medical Center of Southern Nevada
-
Las Vegas, Nevada, Forente stater, 89106
- Cancer and Blood Specialists-Shadow
-
Las Vegas, Nevada, Forente stater, 89109
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
-
Las Vegas, Nevada, Forente stater, 89113
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
-
Las Vegas, Nevada, Forente stater, 89128
- Cancer and Blood Specialists-Tenaya
-
Las Vegas, Nevada, Forente stater, 89128
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
-
Las Vegas, Nevada, Forente stater, 89148-2405
- Las Vegas Cancer Center-Medical Center
-
Las Vegas, Nevada, Forente stater, 89149
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
-
Las Vegas, Nevada, Forente stater, 89128
- Ann M Wierman MD LTD
-
Las Vegas, Nevada, Forente stater, 89074
- Las Vegas Urology - Pecos
-
Las Vegas, Nevada, Forente stater, 89102
- Desert West Surgery
-
Las Vegas, Nevada, Forente stater, 89103
- Hope Cancer Care of Nevada
-
Las Vegas, Nevada, Forente stater, 89106
- Urology Specialists of Nevada - Central
-
Las Vegas, Nevada, Forente stater, 89113
- Las Vegas Prostate Cancer Center
-
Las Vegas, Nevada, Forente stater, 89113
- Las Vegas Urology - Sunset
-
Las Vegas, Nevada, Forente stater, 89128
- Las Vegas Urology - Cathedral Rock
-
Las Vegas, Nevada, Forente stater, 89128
- Las Vegas Urology - Smoke Ranch
-
Las Vegas, Nevada, Forente stater, 89128
- Urology Specialists of Nevada - Northwest
-
Las Vegas, Nevada, Forente stater, 89169
- University Cancer Center
-
Las Vegas, Nevada, Forente stater, 89113
- Urology Specialists of Nevada - Southwest
-
Las Vegas, Nevada, Forente stater, 89128
- Oncology Las Vegas - Tenaya
-
Las Vegas, Nevada, Forente stater, 89183
- OptumCare Cancer Care at Fort Apache
-
Pahrump, Nevada, Forente stater, 89048
- Hope Cancer Care of Nevada-Pahrump
-
Reno, Nevada, Forente stater, 89502
- Renown Regional Medical Center
-
Reno, Nevada, Forente stater, 89503
- Saint Mary's Regional Medical Center
-
Reno, Nevada, Forente stater, 89509
- Radiation Oncology Associates
-
-
New Jersey
-
Hackensack, New Jersey, Forente stater, 07601
- Hackensack University Medical Center
-
Lakewood, New Jersey, Forente stater, 08701
- Monmouth Medical Center Southern Campus
-
Long Branch, New Jersey, Forente stater, 07740
- Monmouth Medical Center
-
Morristown, New Jersey, Forente stater, 07960
- Morristown Medical Center
-
New Brunswick, New Jersey, Forente stater, 08903
- Rutgers Cancer Institute of New Jersey
-
New Brunswick, New Jersey, Forente stater, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
-
New Mexico
-
Albuquerque, New Mexico, Forente stater, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, Forente stater, 12208
- Albany Medical Center
-
Buffalo, New York, Forente stater, 14263
- Roswell Park Cancer Institute
-
New York, New York, Forente stater, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Forente stater, 10029
- Mount Sinai Hospital
-
New York, New York, Forente stater, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, Forente stater, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, Forente stater, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Stony Brook, New York, Forente stater, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, Forente stater, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, Forente stater, 10467
- Montefiore Medical Center - Moses Campus
-
-
North Carolina
-
Chapel Hill, North Carolina, Forente stater, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, Forente stater, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Clinton, North Carolina, Forente stater, 28328
- Southeastern Medical Oncology Center-Clinton
-
Goldsboro, North Carolina, Forente stater, 27534
- Southeastern Medical Oncology Center-Goldsboro
-
Goldsboro, North Carolina, Forente stater, 27534
- Wayne Memorial Hospital
-
Jacksonville, North Carolina, Forente stater, 28546
- Southeastern Medical Oncology Center-Jacksonville
-
Jacksonville, North Carolina, Forente stater, 28546
- Onslow Memorial Hospital
-
-
North Dakota
-
Fargo, North Dakota, Forente stater, 58103
- Essentia Health Cancer Center-South University Clinic
-
Jamestown, North Dakota, Forente stater, 58401
- Essentia Health - Jamestown Clinic
-
-
Ohio
-
Akron, Ohio, Forente stater, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, Forente stater, 45229
- Cincinnati Children's Hospital Medical Center
-
Cincinnati, Ohio, Forente stater, 45220
- Good Samaritan Hospital - Cincinnati
-
Cincinnati, Ohio, Forente stater, 45242
- Bethesda North Hospital
-
Cincinnati, Ohio, Forente stater, 45247
- TriHealth Cancer Institute-Westside
-
Cincinnati, Ohio, Forente stater, 45255
- TriHealth Cancer Institute-Anderson
-
Cleveland, Ohio, Forente stater, 44109
- MetroHealth Medical Center
-
Columbus, Ohio, Forente stater, 43205
- Nationwide Children's Hospital
-
-
Oklahoma
-
Lawton, Oklahoma, Forente stater, 73505
- Cancer Centers of Southwest Oklahoma Research
-
Oklahoma City, Oklahoma, Forente stater, 73104
- University of Oklahoma Health Sciences Center
-
Oklahoma City, Oklahoma, Forente stater, 73120
- Mercy Hospital Oklahoma City
-
Tulsa, Oklahoma, Forente stater, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
-
-
Oregon
-
Baker City, Oregon, Forente stater, 97814
- Saint Alphonsus Cancer Care Center-Baker City
-
Bend, Oregon, Forente stater, 97701
- Saint Charles Health System
-
Clackamas, Oregon, Forente stater, 97015
- Clackamas Radiation Oncology Center
-
Clackamas, Oregon, Forente stater, 97015
- Providence Cancer Institute Clackamas Clinic
-
Coos Bay, Oregon, Forente stater, 97420
- Bay Area Hospital
-
Newberg, Oregon, Forente stater, 97132
- Providence Newberg Medical Center
-
Ontario, Oregon, Forente stater, 97914
- Saint Alphonsus Cancer Care Center-Ontario
-
Oregon City, Oregon, Forente stater, 97045
- Providence Willamette Falls Medical Center
-
Portland, Oregon, Forente stater, 97213
- Providence Portland Medical Center
-
Portland, Oregon, Forente stater, 97225
- Providence Saint Vincent Medical Center
-
Redmond, Oregon, Forente stater, 97756
- Saint Charles Health System-Redmond
-
-
Pennsylvania
-
Hershey, Pennsylvania, Forente stater, 17033-0850
- Penn State Milton S Hershey Medical Center
-
Philadelphia, Pennsylvania, Forente stater, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, Forente stater, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, Forente stater, 19104
- University of Pennsylvania/Abramson Cancer Center
-
-
South Carolina
-
Boiling Springs, South Carolina, Forente stater, 29316
- Prisma Health Cancer Institute - Spartanburg
-
Columbia, South Carolina, Forente stater, 29203
- Prisma Health Richland Hospital
-
Easley, South Carolina, Forente stater, 29640
- Prisma Health Cancer Institute - Easley
-
Greenville, South Carolina, Forente stater, 29605
- Prisma Health Cancer Institute - Faris
-
Greenville, South Carolina, Forente stater, 29607
- Saint Francis Cancer Center
-
Greenville, South Carolina, Forente stater, 29615
- Prisma Health Cancer Institute - Eastside
-
Greenville, South Carolina, Forente stater, 29605
- Prisma Health Cancer Institute - Butternut
-
Greenville, South Carolina, Forente stater, 29601
- Saint Francis Hospital
-
Greenville, South Carolina, Forente stater, 29605
- BI-LO Charities Children's Cancer Center
-
Greenville, South Carolina, Forente stater, 29605
- Prisma Health Greenville Memorial Hospital
-
Greer, South Carolina, Forente stater, 29650
- Prisma Health Cancer Institute - Greer
-
Seneca, South Carolina, Forente stater, 29672
- Prisma Health Cancer Institute - Seneca
-
-
Tennessee
-
Chattanooga, Tennessee, Forente stater, 37404
- Memorial Hospital
-
Hixson, Tennessee, Forente stater, 37343
- Pulmonary Medicine Center of Chattanooga-Hixson
-
Knoxville, Tennessee, Forente stater, 37916
- East Tennessee Childrens Hospital
-
Memphis, Tennessee, Forente stater, 38105
- Saint Jude Children's Research Hospital
-
Nashville, Tennessee, Forente stater, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, Forente stater, 37203
- The Children's Hospital at TriStar Centennial
-
Ooltewah, Tennessee, Forente stater, 37363
- Memorial GYN Plus
-
-
Texas
-
Austin, Texas, Forente stater, 78723
- Dell Children's Medical Center of Central Texas
-
Bryan, Texas, Forente stater, 77802
- Saint Joseph Regional Cancer Center
-
Corpus Christi, Texas, Forente stater, 78411
- Driscoll Children's Hospital
-
El Paso, Texas, Forente stater, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, Forente stater, 76104
- Cook Children's Medical Center
-
San Antonio, Texas, Forente stater, 78207
- Children's Hospital of San Antonio
-
-
Utah
-
American Fork, Utah, Forente stater, 84003
- American Fork Hospital / Huntsman Intermountain Cancer Center
-
Cedar City, Utah, Forente stater, 84720
- Sandra L Maxwell Cancer Center
-
Logan, Utah, Forente stater, 84321
- Logan Regional Hospital
-
Murray, Utah, Forente stater, 84107
- Intermountain Medical Center
-
Ogden, Utah, Forente stater, 84403
- McKay-Dee Hospital Center
-
Riverton, Utah, Forente stater, 84065
- Riverton Hospital
-
Salt Lake City, Utah, Forente stater, 84106
- Utah Cancer Specialists-Salt Lake City
-
Salt Lake City, Utah, Forente stater, 84143
- LDS Hospital
-
St. George, Utah, Forente stater, 84770
- Saint George Regional Medical Center
-
-
Virginia
-
Norfolk, Virginia, Forente stater, 23507
- Children's Hospital of The King's Daughters
-
-
Washington
-
Aberdeen, Washington, Forente stater, 98520
- Providence Regional Cancer System-Aberdeen
-
Auburn, Washington, Forente stater, 98001
- MultiCare Auburn Medical Center
-
Bellevue, Washington, Forente stater, 98004
- Overlake Medical Center
-
Bellingham, Washington, Forente stater, 98225
- PeaceHealth Saint Joseph Medical Center
-
Burien, Washington, Forente stater, 98166
- Saint Anne Hospital
-
Centralia, Washington, Forente stater, 98531
- Providence Regional Cancer System-Centralia
-
Edmonds, Washington, Forente stater, 98026
- Swedish Cancer Institute-Edmonds
-
Enumclaw, Washington, Forente stater, 98022
- Saint Elizabeth Hospital
-
Everett, Washington, Forente stater, 98201
- Providence Regional Cancer Partnership
-
Federal Way, Washington, Forente stater, 98003
- Saint Francis Hospital
-
Gig Harbor, Washington, Forente stater, 98335
- MultiCare Gig Harbor Medical Park
-
Issaquah, Washington, Forente stater, 98029
- Swedish Cancer Institute-Issaquah
-
Kennewick, Washington, Forente stater, 99336
- Kadlec Clinic Hematology and Oncology
-
Lacey, Washington, Forente stater, 98503
- Providence Regional Cancer System-Lacey
-
Lakewood, Washington, Forente stater, 98499
- Saint Clare Hospital
-
Longview, Washington, Forente stater, 98632
- PeaceHealth Saint John Medical Center
-
Port Townsend, Washington, Forente stater, 98368
- Jefferson Healthcare
-
Poulsbo, Washington, Forente stater, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
-
Puyallup, Washington, Forente stater, 98372
- MultiCare Good Samaritan Hospital
-
Renton, Washington, Forente stater, 98055
- Valley Medical Center
-
Seattle, Washington, Forente stater, 98105
- Seattle Children's Hospital
-
Seattle, Washington, Forente stater, 98107
- Swedish Medical Center-Ballard Campus
-
Seattle, Washington, Forente stater, 98122
- Swedish Medical Center-First Hill
-
Seattle, Washington, Forente stater, 98112
- Kaiser Permanente Washington
-
Seattle, Washington, Forente stater, 98104
- Pacific Gynecology Specialists
-
Seattle, Washington, Forente stater, 98122-5711
- Swedish Medical Center-Cherry Hill
-
Sedro-Woolley, Washington, Forente stater, 98284
- PeaceHealth United General Medical Center
-
Shelton, Washington, Forente stater, 98584
- Providence Regional Cancer System-Shelton
-
Silverdale, Washington, Forente stater, 98383
- Saint Joseph Medical Center Hematology and Oncology - Silverdale
-
Spokane, Washington, Forente stater, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Spokane, Washington, Forente stater, 99204
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
-
Spokane, Washington, Forente stater, 99218
- MultiCare Deaconess Cancer and Blood Specialty Center - North
-
Spokane Valley, Washington, Forente stater, 99216
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
-
Tacoma, Washington, Forente stater, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, Forente stater, 98405
- Northwest Medical Specialties PLLC
-
Tacoma, Washington, Forente stater, 98431
- Madigan Army Medical Center
-
Tacoma, Washington, Forente stater, 98405
- MultiCare Tacoma General Hospital
-
Tacoma, Washington, Forente stater, 98405
- Franciscan Research Center-Northwest Medical Plaza
-
Vancouver, Washington, Forente stater, 98664
- PeaceHealth Southwest Medical Center
-
Walla Walla, Washington, Forente stater, 99362
- Providence Saint Mary Regional Cancer Center
-
Yakima, Washington, Forente stater, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
-
Yelm, Washington, Forente stater, 98597
- Providence Regional Cancer System-Yelm
-
-
West Virginia
-
Bridgeport, West Virginia, Forente stater, 26330
- United Hospital Center
-
Martinsburg, West Virginia, Forente stater, 25401
- WVUH-Berkely Medical Center
-
Morgantown, West Virginia, Forente stater, 26506
- West Virginia University Healthcare
-
Parkersburg, West Virginia, Forente stater, 26101
- Camden Clark Medical Center
-
-
Wisconsin
-
Ashland, Wisconsin, Forente stater, 54806
- Duluth Clinic Ashland
-
Ashland, Wisconsin, Forente stater, 54806
- Northwest Wisconsin Cancer Center
-
Burlington, Wisconsin, Forente stater, 53105
- Aurora Cancer Care-Southern Lakes VLCC
-
Chippewa Falls, Wisconsin, Forente stater, 54729
- Marshfield Clinic-Chippewa Center
-
Eau Claire, Wisconsin, Forente stater, 54701
- Marshfield Medical Center-EC Cancer Center
-
Fond du Lac, Wisconsin, Forente stater, 54937
- Aurora Health Center-Fond du Lac
-
Germantown, Wisconsin, Forente stater, 53022
- Aurora Health Care Germantown Health Center
-
Grafton, Wisconsin, Forente stater, 53024
- Aurora Cancer Care-Grafton
-
Green Bay, Wisconsin, Forente stater, 54311
- Aurora BayCare Medical Center
-
Kenosha, Wisconsin, Forente stater, 53142
- Aurora Cancer Care-Kenosha South
-
La Crosse, Wisconsin, Forente stater, 54601
- Gundersen Lutheran Medical Center
-
Ladysmith, Wisconsin, Forente stater, 54848
- Marshfield Medical Center - Ladysmith
-
Madison, Wisconsin, Forente stater, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marinette, Wisconsin, Forente stater, 54143
- Aurora Bay Area Medical Group-Marinette
-
Marshfield, Wisconsin, Forente stater, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, Forente stater, 53226
- Medical College of Wisconsin
-
Milwaukee, Wisconsin, Forente stater, 53209
- Aurora Cancer Care-Milwaukee
-
Milwaukee, Wisconsin, Forente stater, 53215
- Aurora Saint Luke's Medical Center
-
Milwaukee, Wisconsin, Forente stater, 53233
- Aurora Sinai Medical Center
-
Minocqua, Wisconsin, Forente stater, 54548
- Marshfield Medical Center - Minocqua
-
Oshkosh, Wisconsin, Forente stater, 54904
- Vince Lombardi Cancer Clinic - Oshkosh
-
Racine, Wisconsin, Forente stater, 53406
- Aurora Cancer Care-Racine
-
Rice Lake, Wisconsin, Forente stater, 54868
- Marshfield Medical Center-Rice Lake
-
Sheboygan, Wisconsin, Forente stater, 53081
- Vince Lombardi Cancer Clinic-Sheboygan
-
Stevens Point, Wisconsin, Forente stater, 54482
- Marshfield Medical Center-River Region at Stevens Point
-
Summit, Wisconsin, Forente stater, 53066
- Aurora Medical Center in Summit
-
Two Rivers, Wisconsin, Forente stater, 54241
- Vince Lombardi Cancer Clinic-Two Rivers
-
Wausau, Wisconsin, Forente stater, 54401
- Marshfield Clinic-Wausau Center
-
Wauwatosa, Wisconsin, Forente stater, 53226
- Aurora Cancer Care-Milwaukee West
-
West Allis, Wisconsin, Forente stater, 53227
- Aurora West Allis Medical Center
-
Weston, Wisconsin, Forente stater, 54476
- Marshfield Medical Center - Weston
-
Wisconsin Rapids, Wisconsin, Forente stater, 54494
- Marshfield Clinic - Wisconsin Rapids Center
-
-
Wyoming
-
Cheyenne, Wyoming, Forente stater, 82001
- Cheyenne Regional Medical Center-West
-
Cody, Wyoming, Forente stater, 82414
- Billings Clinic-Cody
-
Sheridan, Wyoming, Forente stater, 82801
- Welch Cancer Center
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
-
PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
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Age >= 18 years
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Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
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Patients must have relapsed after first line chemotherapy; may have relapsed after autologous or allogeneic stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; if status post allogeneic stem cell transplant, no active graft versus host disease
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Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients in the nivolumab/brentuximab cohorts ONLY (D, E, F, Y) may have received prior ipilimumab
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Patients may have received other prior activating immunotherapies (i.e. checkpoint inhibitors), but must not have received them within 6 months prior to registration, and there must be no serious unresolved complication of therapy at the time of registration; for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
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Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
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Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
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Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
Patient of childbearing potential and/or sexually active patients must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both single barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
-
Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
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Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
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Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10^9/L) (obtained within 2 weeks prior to registration)
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Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
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Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
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Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
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Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
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No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
-
Patient must have no current or prior history of central nervous system (CNS) involvement
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All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
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No history of Steven's Johnson's syndrome, toxic epidermal necrolysis (TEN)s syndrome, or motor neuropathy
-
Human immunodeficiency virus (HIV) positive patients are allowed on this study if they have a CD4 count > 400, and are on a stable antiviral regimen; patients with poorly controlled HIV or other chronic active viral infections will be excluded
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Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed
- Replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to initiation of study treatment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
- Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
-
Patients must not have grade 2 or greater peripheral sensory neuropathy
-
Patients must not have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
-
Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
-
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
-
Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
-
Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
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Patients registering to Arms D, E, F, G, H, I, X, Y must not currently be smoking tobacco or other substances and must not have smoked within the past 6 months
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RANDOMIZED PHASE II (ARMS K AND L): Age >= 12 years
- Pediatric patients will include any patients < 18 years of age
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have relapsed after first line chemotherapy; may have relapsed after autologous stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; patient must not have received a prior allogeneic stem cell transplant (out of risk of reactivation of pulmonary graft versus host disease [GVHD])
-
RANDOMIZED PHASE II (ARMS K AND L): Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients may not have received prior ipilimumab
-
RANDOMIZED PHASE II (ARMS K AND L): Patients may not have received other prior activating immunotherapies (i.e. checkpoint inhibitor therapies); for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
-
RANDOMIZED PHASE II (ARMS K AND L): Adult patient (>= 18 years of age) ECOG-ACRIN performance status between 0-2
- Pediatric patients (16-17 years of age) must have a Karnofsky performance level >= 50%
- Pediatric patients (12-15 years of age) must have a Lansky performance level >= 50
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RANDOMIZED PHASE II (ARMS K AND L): Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
-
RANDOMIZED PHASE II (ARMS K AND L): Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
RANDOMIZED PHASE II (ARMS K AND L): Patient of childbearing potential and/or sexually active patient must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both double barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
-
RANDOMIZED PHASE II (ARMS K AND L): Patients with impaired decision-making capacity are eligible with legally authorized representative
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RANDOMIZED PHASE II (ARMS K AND L): Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
-
RANDOMIZED PHASE II (ARMS K AND L): ANC >= 1500/mcL (1.5 x 0^9/L) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): AST/ALT =< 2.5 x upper limit of normal (ULN) for age (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Adult patients (>= 18 years old) must have a calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Pediatric patients (< 18 years old) must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine based on age/sex as follows:
-
Age: maximum serum creatinine (mg/dL)
- < 13 years: male (1.2), female (1.2)
- 13 to < 16 years: male (1.5), female (1.4)
- >= 16 years: male (1.7), female (1.4)
-
-
RANDOMIZED PHASE II (ARMS K AND L): No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
-
RANDOMIZED PHASE II (ARMS K AND L): Patient must have no current or prior history of CNS involvement
-
RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
-
RANDOMIZED PHASE II (ARMS K AND L): No history of Steven's Johnson's syndrome, TENs syndrome, or motor neuropathy
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RANDOMIZED PHASE II (ARMS K AND L): HIV positive patients are eligible provided they meet the other protocol criteria including the following:
- Long term survival expected were it not for the cHL
- HIV viral loads undetectable by standard clinical HIV testing
- Willing to adhere to effective combination antiretroviral therapy
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RANDOMIZED PHASE II (ARMS K AND L): Patients must not have autoimmune disorders, prior solid organ transplant, or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of steroid medication for at least 2 weeks prior to initiation of therapy are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have grade 2 or greater peripheral sensory neuropathy
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
-
RANDOMIZED PHASE II (ARMS K AND L): Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not currently be smoking tobacco or other agents; vaping is not allowed
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:
- QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec at baseline
- History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration
- History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
- Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)
- Intra-cardiac defibrillator
- History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
- History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
- Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Phase I Arm I (brentuximab vedotin, ipilimumab)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study. |
Given IV
Andre navn:
Undergo CT
Andre navn:
Undergo biopsy
Andre navn:
Undergo collection of blood
Andre navn:
Given IV
Andre navn:
Undergo PET
Andre navn:
|
|
Eksperimentell: Phase I Arm II (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study. |
Undergo CT
Andre navn:
Undergo biopsy
Andre navn:
Undergo collection of blood
Andre navn:
Given IV
Andre navn:
Undergo PET
Andre navn:
Given IV
Andre navn:
|
|
Eksperimentell: Phase I Arm III (brentuximab vedotin, nivolumab, ipilimumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study. |
Given IV
Andre navn:
Undergo CT
Andre navn:
Undergo biopsy
Andre navn:
Undergo collection of blood
Andre navn:
Given IV
Andre navn:
Undergo PET
Andre navn:
Given IV
Andre navn:
|
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Eksperimentell: Phase II Arm I (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study. |
Undergo CT
Andre navn:
Undergo biopsy
Andre navn:
Undergo collection of blood
Andre navn:
Given IV
Andre navn:
Undergo PET
Andre navn:
Given IV
Andre navn:
|
|
Eksperimentell: Phase II Arm II (brentuximab vedotin, nivolumab, ipilimumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study. |
Given IV
Andre navn:
Undergo CT
Andre navn:
Undergo biopsy
Andre navn:
Undergo collection of blood
Andre navn:
Given IV
Andre navn:
Undergo PET
Andre navn:
Given IV
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum tolerated dose (MTD) of each combination (Phase I)
Tidsramme: 21 days
|
MTD defined as the highest dose level at which less than 33% of 6 patients experience a dose limiting toxicity, will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Upon completion of the trial, frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to CTCAE version 4.0 terminology. Exact 95% confidence intervals (CI) around the toxicity proportions will be calculated. |
21 days
|
|
CR rate (Phase II)
Tidsramme: Up to 10 years
|
The analysis of CR between two arms will be performed using exact Cochran-Mantel-Haenszel (CMH) test stratifying on prior brentuximab vedotin (BV) (yes versus [vs.] no) and age (< 18 vs. >= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. |
Up to 10 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Complete response (CR) rate (Phase I)
Tidsramme: Up to 3 years
|
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI. |
Up to 3 years
|
|
Partial response (PR) rate (Phase I)
Tidsramme: Up to 3 years
|
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI. |
Up to 3 years
|
|
Overall response rate (ORR) rate (Phase I)
Tidsramme: Up to 3 years
|
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI. |
Up to 3 years
|
|
Duration of response (DOR) (Phase I)
Tidsramme: From the documented beginning of response up to 3 years
|
DOR will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. Descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy. |
From the documented beginning of response up to 3 years
|
|
Overall survival (OS) (Phase I)
Tidsramme: From the date of study entry up to 3 years
|
OS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. |
From the date of study entry up to 3 years
|
|
Progression-free survival (PFS) (Phase I)
Tidsramme: From entry onto study up to 3 years
|
PFS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. |
From entry onto study up to 3 years
|
|
ORR (Phase II)
Tidsramme: Up to 10 years
|
Assessed using Revised Response (Cheson) and Deauville criteria. The analysis of ORR between two arms will be performed using the CMH test stratifying on prior BV (yes vs. no) and age (< 18 vs. >= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. |
Up to 10 years
|
|
PFS (or modified PFS) (Phase II)
Tidsramme: From randomization up to 10 years
|
PFS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals. |
From randomization up to 10 years
|
|
OS (Phase II)
Tidsramme: From randomization up to 10 years
|
OS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals. |
From randomization up to 10 years
|
|
DOR (Phase II)
Tidsramme: From the documented beginning of response up to 10 years
|
DOR, will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 90% confidence intervals. The DOR achieved with the most recent prior systemic therapy will be collected on the case report forms, and descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy. |
From the documented beginning of response up to 10 years
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Effekter av kombinasjoner på systemisk immunitet (fase I og II)
Tidsramme: Baseline til opptil 6 uker etter fullført studiebehandling
|
Baseline til opptil 6 uker etter fullført studiebehandling
|
|
|
Change in the percentage of activated T cells and natural killer cells (Phase I and II)
Tidsramme: Baseline (Time 1) to 9 weeks (Time 3, time of first re-staging)
|
These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year versus (vs.) those who are event-free at one year will be evaluated. |
Baseline (Time 1) to 9 weeks (Time 3, time of first re-staging)
|
|
Change in the percentages of activated T cells and natural killer cells (Phase I and II)
Tidsramme: Day 1 of cycle 2 (Time 2) or 9 weeks (Time 3) to up to 6 weeks after completion of study treatment (Time 4, end of study)
|
These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using the Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year vs. those who are event-free at one year will be evaluated. |
Day 1 of cycle 2 (Time 2) or 9 weeks (Time 3) to up to 6 weeks after completion of study treatment (Time 4, end of study)
|
|
Pre- and post-treatment levels of cytokines and T cell specific biomarkers (Phase I and II)
Tidsramme: Baseline to up to 6 weeks after completion of study treatment
|
Pre- and post-treatment levels of these markers will be compared using the Wilcoxon signed-rank test with two-sided type I error of 0.1. Marker levels between patients who fail at 1-year vs. patients who are event-free at 1-year will be evaluated. Given limited data, the analyses of PD-1, co-expression of Tim-3 with PD-1, ICOS, sCD30, galectin-1 and the peripheral blood absolute lymphocyte to monocyte ratio will be mainly exploratory and will be summarized descriptively at the time-points described above. The association with PFS will be explored. |
Baseline to up to 6 weeks after completion of study treatment
|
|
Differentially expressed genes between two groups (patients who fail at 1-year vs. patients who are event-free at 1-year or responders vs. non-responders) (Phase I and II)
Tidsramme: 1 year
|
Assessed using gene expression profiling (GEP). Differentially expressed genes will be identified using a rank-based method developed by Dr. Hong (RankProd, R package, Bioconductor Project) with multiple comparison adjustment using a false discovery rate approach. A two-way unsupervised hierarchical clustering analysis will be applied to both the genes and the samples to illustrate whether GEP can separate two groups or is associated with other clinical factors. The genes ranked as most significant will be assessed by gene ontology and pathway analysis for their potential functions in lymphoma biology and treatment failure. |
1 year
|
|
Microbiome analysis (Phase I and II)
Tidsramme: Completion of study treatment
|
Will compare the gut microbiome between Hodgkin lymphoma (HL) patients and healthy controls with respect to global diversity, taxonomic abundance, and bacterial functional pathways. The relative abundance of each taxon (phyla to genera) and functional pathways among different groups will be statistically compared in univariate analysis using t-test (or Wilcoxon test) and in multivariate analysis using logistic regression. Global diversity tests and multivariate analysis for taxonomic abundance and functional pathways will be adjusted for potential confounders (age, sex, race, and body mass index) in the comparisons of HL patients and controls, and further adjusted for stage and grade when examining the clinical response among HL patients. |
Completion of study treatment
|
|
Absolute maximum standard uptake value (SUVmax) (Phase II)
Tidsramme: Up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, event free survival (EFS), OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (Kaplan-Meier [KM] curve and log-rank testing). |
Up to cycle 10
|
|
Metabolic whole body tumor volume (MTV) and tumor lesion glycolysis (TLG)
Tidsramme: Up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Up to cycle 10
|
|
Percent change in SUVmax, MTV and TLG between baseline and during therapy
Tidsramme: Baseline up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Baseline up to cycle 10
|
|
Percent change in size (sum of perpendicular diameters [SPD]) on computed tomography (CT)
Tidsramme: Baseline up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Baseline up to cycle 10
|
|
Absolute CT tumor volumes
Tidsramme: Up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Up to cycle 10
|
|
Percent change in CT size (SPD) and in CT tumor volume between baseline and during therapy
Tidsramme: Baseline up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Baseline up to cycle 10
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Catherine S Diefenbach, ECOG-ACRIN Cancer Research Group
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Diefenbach CS, Hong F, Ambinder RF, Cohen JB, Robertson MJ, David KA, Advani RH, Fenske TS, Barta SK, Palmisiano ND, Svoboda J, Morgan DS, Karmali R, Sharon E, Streicher H, Kahl BS, Ansell SM. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020 Sep;7(9):e660-e670. doi: 10.1016/S2352-3026(20)30221-0.
- Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
- Gonzalez-Kozlova E, Huang HH, Jagede OA, Tuballes K, Del Valle DM, Kelly G, Patel M, Xie H, Harris J, Argueta K, Nie K, Barcessat V, Moravec R, Altreuter J, Duose DY, Kahl BS, Ansell SM, Yu J, Cerami E, Lindsay JR, Wistuba II, Kim-Schulze S, Diefenbach CS, Gnjatic S. Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma. Cancer Res Commun. 2024 Jul 1;4(7):1726-1737. doi: 10.1158/2767-9764.CRC-24-0252.
- Mu-Mosley H, von Itzstein MS, Fattah F, Liu J, Zhu C, Xie Y, Wakeland EK, Park JY, Kahl BS, Diefenbach CS, Gerber DE. Distinct autoantibody profiles across checkpoint inhibitor types and toxicities. Oncoimmunology. 2024 May 9;13(1):2351255. doi: 10.1080/2162402X.2024.2351255. eCollection 2024.
- Diefenbach CS, Jegede O, Wang V, Ansell SM, Kostakoglu L, Steidl C, Natkunam Y, Scott DW, Ambinder RF, David KA, Advani RH, Bartlett NL, Robertson MJ, Thomas SP, Cohen J, Ibrahimi S, Goyal G, Mehta-Shah N, Amengual JE, Forlenza CJ, Cole PD, Duan F, Kelly K, Kahl BS. A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma. Blood. 2026 Apr 30;147(18):2041-2052. doi: 10.1182/blood.2025029546.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Antatt)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Peptider
- Aminosyrer, peptider og proteiner
- Oligopeptider
- Proteiner
- Undersøkelsesteknikker
- Kliniske laboratorieteknikker
- Diagnostiske teknikker og prosedyrer
- Diagnose
- Kirurgiske prosedyrer, operativ
- Cytologiske teknikker
- Cytodiagnose
- Biologiske faktorer
- Antistoffer, monoklonalt, humanisert
- Antistoffer, monoklonalt
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Diagnostiske teknikker, kirurgisk
- Kjemisteknikker, analytisk
- Spektrumanalyse
- Reseptorer, celleoverflate
- Membranproteiner
- Antigener
- Antigener, overflate
- Biomarkører
- Reseptorer, immunologisk
- Antigener, differensiering, T-lymfocytt
- Antigener, differensiering
- Immunsjekkpunktproteiner
- Kostimulerende og hemmende T-celle reseptorer
- Nivolumab
- Ipilimumab
- Brentuximab Vedotin
- Biopsi
- Prøvehåndtering
- Magnetisk resonansspektroskopi
- CTLA-4 antigen
Andre studie-ID-numre
- NCI-2013-01275
- U10CA180820 (U.S. NIH-stipend/kontrakt)
- U24CA196172 (U.S. NIH-stipend/kontrakt)
- NCI-2013-01275 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
- E4412 (Annen identifikator: CTEP)
- S14-00011
- E4412
- E4412 (Annen identifikator: ECOG-ACRIN Cancer Research Group)
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