Brentuximab Vedotin en Nivolumab met of zonder ipilimumab bij de behandeling van patiënten met recidiverend of refractair Hodgkin-lymfoom
Een fase I-studie met een uitbreidingscohort/gerandomiseerde fase II-studie van de combinaties van ipilimumab, nivolumab en brentuximab Vedotin bij patiënten met recidiverend/refractair hodgkinlymfoom
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.
Studie Overzicht
Toestand
Gedetailleerde beschrijving
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
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
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Alabama
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Birmingham, Alabama, Verenigde Staten, 35233
- University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, Verenigde Staten, 35233
- Children's Hospital of Alabama
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Alaska
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Anchorage, Alaska, Verenigde Staten, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Verenigde Staten, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Verenigde Staten, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Verenigde Staten, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Verenigde Staten, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Verenigde Staten, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Verenigde Staten, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Verenigde Staten, 99504
- Anchorage Radiation Therapy Center
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Fairbanks, Alaska, Verenigde Staten, 99701
- Fairbanks Memorial Hospital
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Arizona
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Kingman, Arizona, Verenigde Staten, 86401
- Kingman Regional Medical Center
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Phoenix, Arizona, Verenigde Staten, 85004
- Cancer Center at Saint Joseph's
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Arkansas
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Fort Smith, Arkansas, Verenigde Staten, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, Verenigde Staten, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Antioch, California, Verenigde Staten, 94531
- Kaiser Permanente-Deer Valley Medical Center
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Arroyo Grande, California, Verenigde Staten, 93420
- PCR Oncology
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Arroyo Grande, California, Verenigde Staten, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, Verenigde Staten, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Dublin, California, Verenigde Staten, 94568
- Kaiser Permanente Dublin
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Fremont, California, Verenigde Staten, 94538
- Kaiser Permanente-Fremont
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Fresno, California, Verenigde Staten, 93720
- Kaiser Permanente-Fresno
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Fresno, California, Verenigde Staten, 93720
- Fresno Cancer Center
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Modesto, California, Verenigde Staten, 95356
- Kaiser Permanente-Modesto
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Oakland, California, Verenigde Staten, 94611
- Kaiser Permanente-Oakland
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Oakland, California, Verenigde Staten, 94611
- Kaiser Permanente Oakland-Broadway
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Orange, California, Verenigde Staten, 92868
- Children's Hospital of Orange County
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Palo Alto, California, Verenigde Staten, 94304
- Stanford Cancer Institute Palo Alto
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Rancho Cordova, California, Verenigde Staten, 95670
- Kaiser Permanente-Rancho Cordova Cancer Center
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Redwood City, California, Verenigde Staten, 94063
- Kaiser Permanente-Redwood City
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Richmond, California, Verenigde Staten, 94801
- Kaiser Permanente-Richmond
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Rohnert Park, California, Verenigde Staten, 94928
- Rohnert Park Cancer Center
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Roseville, California, Verenigde Staten, 95678
- The Permanente Medical Group-Roseville Radiation Oncology
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Roseville, California, Verenigde Staten, 95661
- Kaiser Permanente-Roseville
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Sacramento, California, Verenigde Staten, 95814
- Kaiser Permanente Downtown Commons
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Sacramento, California, Verenigde Staten, 95823
- Kaiser Permanente-South Sacramento
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Sacramento, California, Verenigde Staten, 95823
- South Sacramento Cancer Center
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Sacramento, California, Verenigde Staten, 95825
- Kaiser Permanente Sacramento Medical Center
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San Francisco, California, Verenigde Staten, 94115
- Kaiser Permanente-San Francisco
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San Francisco, California, Verenigde Staten, 94158
- UCSF Medical Center-Mission Bay
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San Jose, California, Verenigde Staten, 95119
- Kaiser Permanente-Santa Teresa-San Jose
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San Leandro, California, Verenigde Staten, 94577
- Kaiser Permanente San Leandro
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San Luis Obispo, California, Verenigde Staten, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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San Rafael, California, Verenigde Staten, 94903
- Kaiser San Rafael-Gallinas
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San Rafael, California, Verenigde Staten, 94903
- Kaiser Permanente-San Rafael
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Santa Clara, California, Verenigde Staten, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Maria, California, Verenigde Staten, 93444
- Mission Hope Medical Oncology - Santa Maria
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Santa Rosa, California, Verenigde Staten, 95403
- Kaiser Permanente-Santa Rosa
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South San Francisco, California, Verenigde Staten, 94080
- Kaiser Permanente Cancer Treatment Center
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South San Francisco, California, Verenigde Staten, 94080
- Kaiser Permanente-South San Francisco
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Stockton, California, Verenigde Staten, 95210
- Kaiser Permanente-Stockton
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Vacaville, California, Verenigde Staten, 95688
- Kaiser Permanente Medical Center-Vacaville
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Vallejo, California, Verenigde Staten, 94589
- Kaiser Permanente-Vallejo
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Walnut Creek, California, Verenigde Staten, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Verenigde Staten, 80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora, Colorado, Verenigde Staten, 80012
- The Medical Center of Aurora
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Boulder, Colorado, Verenigde Staten, 80303
- Boulder Community Foothills Hospital
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Boulder, Colorado, Verenigde Staten, 80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial, Colorado, Verenigde Staten, 80112
- Rocky Mountain Cancer Centers - Centennial
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Colorado Springs, Colorado, Verenigde Staten, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, Verenigde Staten, 80907
- Rocky Mountain Cancer Centers-Penrose
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Denver, Colorado, Verenigde Staten, 80218
- Presbyterian - Saint Lukes Medical Center - Health One
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Denver, Colorado, Verenigde Staten, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Denver, Colorado, Verenigde Staten, 80220
- Rose Medical Center
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Denver, Colorado, Verenigde Staten, 80218
- Rocky Mountain Cancer Centers-Midtown
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Denver, Colorado, Verenigde Staten, 80220
- Rocky Mountain Cancer Centers-Rose
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Denver, Colorado, Verenigde Staten, 80204
- Denver Health Medical Center
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Denver, Colorado, Verenigde Staten, 80218
- Colorado Blood Cancer Institute
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Denver, Colorado, Verenigde Staten, 80204
- Cancer Center of Colorado at Sloan's Lake
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Denver, Colorado, Verenigde Staten, 80209
- The Women's Imaging Center
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Denver, Colorado, Verenigde Staten, 80206
- National Jewish Health-Main Campus
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Denver, Colorado, Verenigde Staten, 80220
- Western Surgical Care
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Denver, Colorado, Verenigde Staten, 80218
- Saint Joseph Hospital - Cancer Centers of Colorado
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Denver, Colorado, Verenigde Staten, 80210
- AdventHealth Porter
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Durango, Colorado, Verenigde Staten, 81301
- Mercy Medical Center
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Durango, Colorado, Verenigde Staten, 81301
- CommonSpirit Cancer Center Mercy
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Englewood, Colorado, Verenigde Staten, 80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood, Colorado, Verenigde Staten, 80113
- Swedish Medical Center
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Englewood, Colorado, Verenigde Staten, 80113
- Rocky Mountain Cancer Centers - Swedish
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Golden, Colorado, Verenigde Staten, 80401
- Mountain Blue Cancer Care Center
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Golden, Colorado, Verenigde Staten, 80401
- National Jewish Health-Western Hematology Oncology
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Grand Junction, Colorado, Verenigde Staten, 81501
- Saint Mary's Hospital and Regional Medical Center
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Greeley, Colorado, Verenigde Staten, 80631
- Banner North Colorado Medical Center
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Lafayette, Colorado, Verenigde Staten, 80026
- Good Samaritan Hospital - Cancer Centers of Colorado
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Lakewood, Colorado, Verenigde Staten, 80228
- Rocky Mountain Cancer Centers-Lakewood
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Lakewood, Colorado, Verenigde Staten, 80228
- CommonSpirit Saint Anthony Hospital Cancer Center
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Littleton, Colorado, Verenigde Staten, 80120
- Rocky Mountain Cancer Centers-Littleton
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Littleton, Colorado, Verenigde Staten, 80122
- AdventHealth Littleton
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Lone Tree, Colorado, Verenigde Staten, 80124
- Sky Ridge Medical Center
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Lone Tree, Colorado, Verenigde Staten, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
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Longmont, Colorado, Verenigde Staten, 80501
- Longmont United Hospital
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Longmont, Colorado, Verenigde Staten, 80501
- Rocky Mountain Cancer Centers-Longmont
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Loveland, Colorado, Verenigde Staten, 80539
- Banner North Colorado Medical Center - Loveland Campus
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Parker, Colorado, Verenigde Staten, 80138
- Rocky Mountain Cancer Centers-Parker
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Parker, Colorado, Verenigde Staten, 80138
- AdventHealth Parker
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Pueblo, Colorado, Verenigde Staten, 81008
- Rocky Mountain Cancer Centers - Pueblo
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Thornton, Colorado, Verenigde Staten, 80260
- Rocky Mountain Cancer Centers-Thornton
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Thornton, Colorado, Verenigde Staten, 80260
- National Jewish Health-Northern Hematology Oncology
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Wheat Ridge, Colorado, Verenigde Staten, 80401
- Intermountain Health Lutheran Hospital
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District of Columbia
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Washington D.C., District of Columbia, Verenigde Staten, 20010
- Children's National Medical Center
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Florida
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Fort Myers, Florida, Verenigde Staten, 33905
- Regional Cancer Center-Lee Memorial Health System
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Fort Myers, Florida, Verenigde Staten, 33908
- Golisano Children's Hospital of Southwest Florida
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St. Petersburg, Florida, Verenigde Staten, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, Verenigde Staten, 33606
- Tampa General Hospital
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Tampa, Florida, Verenigde Staten, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory University Hospital/Winship Cancer Institute
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Atlanta, Georgia, Verenigde Staten, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
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Hawaii
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Honolulu, Hawaii, Verenigde Staten, 96819
- Kaiser Permanente Moanalua Medical Center
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Idaho
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Boise, Idaho, Verenigde Staten, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, Verenigde Staten, 83712
- Saint Luke's Cancer Institute - Boise
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Caldwell, Idaho, Verenigde Staten, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Verenigde Staten, 83814
- Kootenai Health - Coeur d'Alene
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Emmett, Idaho, Verenigde Staten, 83617
- Walter Knox Memorial Hospital
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Fruitland, Idaho, Verenigde Staten, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Verenigde Staten, 83642
- Idaho Urologic Institute-Meridian
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Meridian, Idaho, Verenigde Staten, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Verenigde Staten, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Nampa, Idaho, Verenigde Staten, 83687
- Saint Luke's Cancer Institute - Nampa
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Post Falls, Idaho, Verenigde Staten, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Verenigde Staten, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Twin Falls, Idaho, Verenigde Staten, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, Verenigde Staten, 62002
- OSF Saint Anthony's Health Center
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Aurora, Illinois, Verenigde Staten, 60504
- Rush-Copley Medical Center
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Bloomington, Illinois, Verenigde Staten, 61704
- Illinois CancerCare-Bloomington
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Canton, Illinois, Verenigde Staten, 61520
- Illinois CancerCare-Canton
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Carbondale, Illinois, Verenigde Staten, 62902
- Memorial Hospital of Carbondale
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Carterville, Illinois, Verenigde Staten, 62918
- SIH Cancer Institute
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Carthage, Illinois, Verenigde Staten, 62321
- Illinois CancerCare-Carthage
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Centralia, Illinois, Verenigde Staten, 62801
- Centralia Oncology Clinic
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Chicago, Illinois, Verenigde Staten, 60611
- Northwestern University
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Chicago, Illinois, Verenigde Staten, 60612
- University of Illinois
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Chicago, Illinois, Verenigde Staten, 60612
- Rush MD Anderson Cancer Center
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Danville, Illinois, Verenigde Staten, 61832
- Carle at The Riverfront
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Decatur, Illinois, Verenigde Staten, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Verenigde Staten, 62526
- Cancer Care Specialists of Illinois - Decatur
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Dixon, Illinois, Verenigde Staten, 61021
- Illinois CancerCare-Dixon
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Effingham, Illinois, Verenigde Staten, 62401
- Crossroads Cancer Center
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Effingham, Illinois, Verenigde Staten, 62401
- Carle Physician Group-Effingham
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Eureka, Illinois, Verenigde Staten, 61530
- Illinois CancerCare-Eureka
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Galesburg, Illinois, Verenigde Staten, 61401
- Western Illinois Cancer Treatment Center
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Galesburg, Illinois, Verenigde Staten, 61401
- Illinois CancerCare-Galesburg
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Joliet, Illinois, Verenigde Staten, 60435
- Duly Health and Care Joliet
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Kewanee, Illinois, Verenigde Staten, 61443
- Illinois CancerCare-Kewanee Clinic
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Macomb, Illinois, Verenigde Staten, 61455
- Illinois CancerCare-Macomb
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Mattoon, Illinois, Verenigde Staten, 61938
- Carle Physician Group-Mattoon/Charleston
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Mount Vernon, Illinois, Verenigde Staten, 62864
- SSM Health Good Samaritan
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O'Fallon, Illinois, Verenigde Staten, 62269
- Cancer Care Center of O'Fallon
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Ottawa, Illinois, Verenigde Staten, 61350
- Illinois CancerCare-Ottawa Clinic
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Pekin, Illinois, Verenigde Staten, 61554
- Illinois CancerCare-Pekin
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Peoria, Illinois, Verenigde Staten, 61636
- Methodist Medical Center of Illinois
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Peoria, Illinois, Verenigde Staten, 61615
- Illinois CancerCare-Peoria
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Peru, Illinois, Verenigde Staten, 61354
- Illinois CancerCare-Peru
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Peru, Illinois, Verenigde Staten, 61354
- Valley Radiation Oncology
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Princeton, Illinois, Verenigde Staten, 61356
- Illinois CancerCare-Princeton
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Springfield, Illinois, Verenigde Staten, 62702
- Southern Illinois University School of Medicine
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Springfield, Illinois, Verenigde Staten, 62702
- Springfield Clinic
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Springfield, Illinois, Verenigde Staten, 62781
- Springfield Memorial Hospital
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Swansea, Illinois, Verenigde Staten, 62226
- Southwest Illinois Health Services LLP
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Urbana, Illinois, Verenigde Staten, 61801
- Carle Cancer Center
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Urbana, Illinois, Verenigde Staten, 61801
- The Carle Foundation Hospital
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Washington, Illinois, Verenigde Staten, 61571
- Illinois CancerCare - Washington
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Yorkville, Illinois, Verenigde Staten, 60560
- Rush-Copley Healthcare Center
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Indiana
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Evansville, Indiana, Verenigde Staten, 47713
- Deaconess Clinic Downtown
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Indianapolis, Indiana, Verenigde Staten, 46202
- Indiana University/Melvin and Bren Simon Cancer Center
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Newburgh, Indiana, Verenigde Staten, 47630
- Chancellor Center for Oncology
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Iowa
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Clive, Iowa, Verenigde Staten, 50325
- Mercy Cancer Center-West Lakes
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Clive, Iowa, Verenigde Staten, 50325
- UI Health Care Mission Cancer and Blood - West Des Moines Clinic
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Council Bluffs, Iowa, Verenigde Staten, 51503
- Alegent Health Mercy Hospital
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Creston, Iowa, Verenigde Staten, 50801
- Greater Regional Medical Center
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Des Moines, Iowa, Verenigde Staten, 50314
- Mercy Medical Center - Des Moines
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Des Moines, Iowa, Verenigde Staten, 50314
- UI Health Care Mission Cancer and Blood - Laurel Clinic
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West Des Moines, Iowa, Verenigde Staten, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, Verenigde Staten, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, Verenigde Staten, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, Verenigde Staten, 40004
- CommonSpirit Saint Joseph Hospital - Bardstown
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Corbin, Kentucky, Verenigde Staten, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, Verenigde Staten, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, Verenigde Staten, 40509
- CommonSpirit Saint Joseph Medical Center - East Lexington
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London, Kentucky, Verenigde Staten, 40741
- CommonSpirit Saint Joseph Hospital London
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Louisville, Kentucky, Verenigde Staten, 40202
- Jewish Hospital
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Louisville, Kentucky, Verenigde Staten, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, Verenigde Staten, 40215
- Saints Mary and Elizabeth Hospital
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Paducah, Kentucky, Verenigde Staten, 42003
- Mercy Health - Paducah Cancer Center
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Shepherdsville, Kentucky, Verenigde Staten, 40165
- Jewish Hospital Medical Center South
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Louisiana
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Baton Rouge, Louisiana, Verenigde Staten, 70805
- LSU Health Baton Rouge-North Clinic
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Baton Rouge, Louisiana, Verenigde Staten, 70809
- Louisiana Hematology Oncology Associates LLC
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Baton Rouge, Louisiana, Verenigde Staten, 70809
- Mary Bird Perkins Cancer Center
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Baton Rouge, Louisiana, Verenigde Staten, 70808
- Our Lady of The Lake
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Baton Rouge, Louisiana, Verenigde Staten, 70808
- Our Lady of the Lake Physician Group
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Covington, Louisiana, Verenigde Staten, 70433
- Northshore Oncology Associates-Covington
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Houma, Louisiana, Verenigde Staten, 70360
- Terrebonne General Medical Center
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Houma, Louisiana, Verenigde Staten, 70360
- Oncology Center of The South Incorporated
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, Verenigde Staten, 21229
- Saint Agnes Hospital
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Bethesda, Maryland, Verenigde Staten, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02111
- Tufts Medical Center
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Michigan
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Port Huron, Michigan, Verenigde Staten, 48060
- Lake Huron Medical Center
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Port Huron, Michigan, Verenigde Staten, 48060
- Huron Medical Center PC
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Minnesota
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Aitkin, Minnesota, Verenigde Staten, 56431
- Riverwood Healthcare Center
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Brainerd, Minnesota, Verenigde Staten, 56401
- Essentia Health Saint Joseph's Medical Center
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Deer River, Minnesota, Verenigde Staten, 56636
- Essentia Health - Deer River Clinic
-
Detroit Lakes, Minnesota, Verenigde Staten, 56501
- Essentia Health Saint Mary's - Detroit Lakes Clinic
-
Duluth, Minnesota, Verenigde Staten, 55805
- Essentia Health Cancer Center
-
Duluth, Minnesota, Verenigde Staten, 55805
- Essentia Health Saint Mary's Medical Center
-
Duluth, Minnesota, Verenigde Staten, 55805
- Miller-Dwan Hospital
-
Fergus Falls, Minnesota, Verenigde Staten, 56537
- Lake Region Healthcare Corporation-Cancer Care
-
Fosston, Minnesota, Verenigde Staten, 56542
- Essentia Health - Fosston
-
Hibbing, Minnesota, Verenigde Staten, 55746
- Essentia Health Hibbing Clinic
-
Park Rapids, Minnesota, Verenigde Staten, 56470
- Essentia Health - Park Rapids
-
Rochester, Minnesota, Verenigde Staten, 55905
- Mayo Clinic in Rochester
-
Sandstone, Minnesota, Verenigde Staten, 55072
- Essentia Health Sandstone
-
Virginia, Minnesota, Verenigde Staten, 55792
- Essentia Health Virginia Clinic
-
-
Missouri
-
Ballwin, Missouri, Verenigde Staten, 63011
- Mercy Oncology and Hematology - Clayton-Clarkson
-
Bolivar, Missouri, Verenigde Staten, 65613
- Central Care Cancer Center - Bolivar
-
Bonne Terre, Missouri, Verenigde Staten, 63628
- Parkland Health Center-Bonne Terre
-
Branson, Missouri, Verenigde Staten, 65616
- Cox Cancer Center Branson
-
Cape Girardeau, Missouri, Verenigde Staten, 63703
- Saint Francis Medical Center
-
Cape Girardeau, Missouri, Verenigde Staten, 63703
- Mercy Cancer Center - Cape Girardeau
-
Chesterfield, Missouri, Verenigde Staten, 63017
- Saint Luke's Hospital
-
City of Saint Peters, Missouri, Verenigde Staten, 63376
- Siteman Cancer Center at Saint Peters Hospital
-
Creve Coeur, Missouri, Verenigde Staten, 63141
- Siteman Cancer Center at West County Hospital
-
Farmington, Missouri, Verenigde Staten, 63640
- Parkland Health Center - Farmington
-
Jefferson City, Missouri, Verenigde Staten, 65109
- MU Health Care Goldschmidt Cancer Center
-
Joplin, Missouri, Verenigde Staten, 64804
- Freeman Health System
-
Joplin, Missouri, Verenigde Staten, 64804
- Mercy Hospital Joplin
-
Kansas City, Missouri, Verenigde Staten, 64108
- Children's Mercy Hospitals and Clinics
-
Rolla, Missouri, Verenigde Staten, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
-
Rolla, Missouri, Verenigde Staten, 65401
- Phelps Health Delbert Day Cancer Institute
-
Saint Joseph, Missouri, Verenigde Staten, 64506
- Heartland Regional Medical Center
-
Sainte Genevieve, Missouri, Verenigde Staten, 63670
- Sainte Genevieve County Memorial Hospital
-
Springfield, Missouri, Verenigde Staten, 65807
- CoxHealth South Hospital
-
Springfield, Missouri, Verenigde Staten, 65804
- Mercy Hospital Springfield
-
St Louis, Missouri, Verenigde Staten, 63110
- Washington University School of Medicine
-
St Louis, Missouri, Verenigde Staten, 63129
- Siteman Cancer Center-South County
-
St Louis, Missouri, Verenigde Staten, 63136
- Siteman Cancer Center at Christian Hospital
-
St Louis, Missouri, Verenigde Staten, 63131
- Missouri Baptist Medical Center
-
St Louis, Missouri, Verenigde Staten, 63109
- Mercy Infusion Center - Chippewa
-
St Louis, Missouri, Verenigde Staten, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, Verenigde Staten, 63128
- Mercy Hospital South
-
Sullivan, Missouri, Verenigde Staten, 63080
- Missouri Baptist Sullivan Hospital
-
Washington, Missouri, Verenigde Staten, 63090
- Mercy Hospital Washington
-
-
Montana
-
Anaconda, Montana, Verenigde Staten, 59711
- Community Hospital of Anaconda
-
Billings, Montana, Verenigde Staten, 59101
- Billings Clinic Cancer Center
-
Billings, Montana, Verenigde Staten, 59101
- Saint Vincent Healthcare
-
Billings, Montana, Verenigde Staten, 59102
- Saint Vincent Frontier Cancer Center
-
Bozeman, Montana, Verenigde Staten, 59715
- Bozeman Health Deaconess Hospital
-
Butte, Montana, Verenigde Staten, 59701
- Saint James Community Hospital and Cancer Treatment Center
-
Great Falls, Montana, Verenigde Staten, 59405
- Great Falls Clinic
-
Great Falls, Montana, Verenigde Staten, 59405
- Benefis Sletten Cancer Institute
-
Helena, Montana, Verenigde Staten, 59601
- Saint Peter's Community Hospital
-
Kalispell, Montana, Verenigde Staten, 59901
- Logan Health Medical Center
-
Missoula, Montana, Verenigde Staten, 59802
- Saint Patrick Hospital - Community Hospital
-
Missoula, Montana, Verenigde Staten, 59804
- Community Medical Center
-
-
Nebraska
-
Grand Island, Nebraska, Verenigde Staten, 68803
- Nebraska Cancer Specialists/Oncology Hematology West PC
-
Kearney, Nebraska, Verenigde Staten, 68847
- CHI Health Good Samaritan
-
Kearney, Nebraska, Verenigde Staten, 68845
- Fred and Pamela Buffett Cancer Center - Kearney
-
Lincoln, Nebraska, Verenigde Staten, 68510
- Saint Elizabeth Regional Medical Center
-
Omaha, Nebraska, Verenigde Staten, 68124
- Alegent Health Bergan Mercy Medical Center
-
Omaha, Nebraska, Verenigde Staten, 68122
- Alegent Health Immanuel Medical Center
-
Omaha, Nebraska, Verenigde Staten, 68130
- Alegent Health Lakeside Hospital
-
Omaha, Nebraska, Verenigde Staten, 68122
- Hematology and Oncology Consultants PC
-
Papillion, Nebraska, Verenigde Staten, 68046
- Midlands Community Hospital
-
-
Nevada
-
Carson City, Nevada, Verenigde Staten, 89703
- Carson Tahoe Regional Medical Center
-
Henderson, Nevada, Verenigde Staten, 89052
- Comprehensive Cancer Centers of Nevada - Henderson
-
Henderson, Nevada, Verenigde Staten, 89052
- Cancer and Blood Specialists-Henderson
-
Henderson, Nevada, Verenigde Staten, 89052
- Las Vegas Cancer Center-Henderson
-
Henderson, Nevada, Verenigde Staten, 89074
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
-
Henderson, Nevada, Verenigde Staten, 89052
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
-
Henderson, Nevada, Verenigde Staten, 89074
- Las Vegas Urology - Green Valley
-
Henderson, Nevada, Verenigde Staten, 89074
- Las Vegas Urology - Pebble
-
Henderson, Nevada, Verenigde Staten, 89074
- Urology Specialists of Nevada - Green Valley
-
Henderson, Nevada, Verenigde Staten, 89074
- Oncology Las Vegas - Henderson
-
Las Vegas, Nevada, Verenigde Staten, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, Verenigde Staten, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, Verenigde Staten, 89102
- OptumCare Cancer Care at Charleston
-
Las Vegas, Nevada, Verenigde Staten, 89106
- Radiation Oncology Centers of Nevada Central
-
Las Vegas, Nevada, Verenigde Staten, 89119
- Radiation Oncology Centers of Nevada Southeast
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Comprehensive Cancer Centers of Nevada - Northwest
-
Las Vegas, Nevada, Verenigde Staten, 89128
- OptumCare Cancer Care at MountainView
-
Las Vegas, Nevada, Verenigde Staten, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, Verenigde Staten, 89144
- Comprehensive Cancer Centers of Nevada - Town Center
-
Las Vegas, Nevada, Verenigde Staten, 89144
- Comprehensive Cancer Centers of Nevada-Summerlin
-
Las Vegas, Nevada, Verenigde Staten, 89148
- Comprehensive Cancer Centers of Nevada
-
Las Vegas, Nevada, Verenigde Staten, 89169
- Comprehensive Cancer Centers of Nevada - Central Valley
-
Las Vegas, Nevada, Verenigde Staten, 89102
- University Medical Center of Southern Nevada
-
Las Vegas, Nevada, Verenigde Staten, 89106
- Cancer and Blood Specialists-Shadow
-
Las Vegas, Nevada, Verenigde Staten, 89109
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
-
Las Vegas, Nevada, Verenigde Staten, 89113
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Cancer and Blood Specialists-Tenaya
-
Las Vegas, Nevada, Verenigde Staten, 89128
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
-
Las Vegas, Nevada, Verenigde Staten, 89148-2405
- Las Vegas Cancer Center-Medical Center
-
Las Vegas, Nevada, Verenigde Staten, 89149
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Ann M Wierman MD LTD
-
Las Vegas, Nevada, Verenigde Staten, 89074
- Las Vegas Urology - Pecos
-
Las Vegas, Nevada, Verenigde Staten, 89102
- Desert West Surgery
-
Las Vegas, Nevada, Verenigde Staten, 89103
- Hope Cancer Care of Nevada
-
Las Vegas, Nevada, Verenigde Staten, 89106
- Urology Specialists of Nevada - Central
-
Las Vegas, Nevada, Verenigde Staten, 89113
- Las Vegas Prostate Cancer Center
-
Las Vegas, Nevada, Verenigde Staten, 89113
- Las Vegas Urology - Sunset
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Las Vegas Urology - Cathedral Rock
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Las Vegas Urology - Smoke Ranch
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Urology Specialists of Nevada - Northwest
-
Las Vegas, Nevada, Verenigde Staten, 89169
- University Cancer Center
-
Las Vegas, Nevada, Verenigde Staten, 89113
- Urology Specialists of Nevada - Southwest
-
Las Vegas, Nevada, Verenigde Staten, 89128
- Oncology Las Vegas - Tenaya
-
Las Vegas, Nevada, Verenigde Staten, 89183
- OptumCare Cancer Care at Fort Apache
-
Pahrump, Nevada, Verenigde Staten, 89048
- Hope Cancer Care of Nevada-Pahrump
-
Reno, Nevada, Verenigde Staten, 89502
- Renown Regional Medical Center
-
Reno, Nevada, Verenigde Staten, 89503
- Saint Mary's Regional Medical Center
-
Reno, Nevada, Verenigde Staten, 89509
- Radiation Oncology Associates
-
-
New Jersey
-
Hackensack, New Jersey, Verenigde Staten, 07601
- Hackensack University Medical Center
-
Lakewood, New Jersey, Verenigde Staten, 08701
- Monmouth Medical Center Southern Campus
-
Long Branch, New Jersey, Verenigde Staten, 07740
- Monmouth Medical Center
-
Morristown, New Jersey, Verenigde Staten, 07960
- Morristown Medical Center
-
New Brunswick, New Jersey, Verenigde Staten, 08903
- Rutgers Cancer Institute of New Jersey
-
New Brunswick, New Jersey, Verenigde Staten, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
-
New Mexico
-
Albuquerque, New Mexico, Verenigde Staten, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, Verenigde Staten, 12208
- Albany Medical Center
-
Buffalo, New York, Verenigde Staten, 14263
- Roswell Park Cancer Institute
-
New York, New York, Verenigde Staten, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Verenigde Staten, 10029
- Mount Sinai Hospital
-
New York, New York, Verenigde Staten, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, Verenigde Staten, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, Verenigde Staten, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Stony Brook, New York, Verenigde Staten, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, Verenigde Staten, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, Verenigde Staten, 10467
- Montefiore Medical Center - Moses Campus
-
-
North Carolina
-
Chapel Hill, North Carolina, Verenigde Staten, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, Verenigde Staten, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Clinton, North Carolina, Verenigde Staten, 28328
- Southeastern Medical Oncology Center-Clinton
-
Goldsboro, North Carolina, Verenigde Staten, 27534
- Southeastern Medical Oncology Center-Goldsboro
-
Goldsboro, North Carolina, Verenigde Staten, 27534
- Wayne Memorial Hospital
-
Jacksonville, North Carolina, Verenigde Staten, 28546
- Southeastern Medical Oncology Center-Jacksonville
-
Jacksonville, North Carolina, Verenigde Staten, 28546
- Onslow Memorial Hospital
-
-
North Dakota
-
Fargo, North Dakota, Verenigde Staten, 58103
- Essentia Health Cancer Center-South University Clinic
-
Jamestown, North Dakota, Verenigde Staten, 58401
- Essentia Health - Jamestown Clinic
-
-
Ohio
-
Akron, Ohio, Verenigde Staten, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, Verenigde Staten, 45229
- Cincinnati Children's Hospital Medical Center
-
Cincinnati, Ohio, Verenigde Staten, 45220
- Good Samaritan Hospital - Cincinnati
-
Cincinnati, Ohio, Verenigde Staten, 45242
- Bethesda North Hospital
-
Cincinnati, Ohio, Verenigde Staten, 45247
- TriHealth Cancer Institute-Westside
-
Cincinnati, Ohio, Verenigde Staten, 45255
- TriHealth Cancer Institute-Anderson
-
Cleveland, Ohio, Verenigde Staten, 44109
- MetroHealth Medical Center
-
Columbus, Ohio, Verenigde Staten, 43205
- Nationwide Children's Hospital
-
-
Oklahoma
-
Lawton, Oklahoma, Verenigde Staten, 73505
- Cancer Centers of Southwest Oklahoma Research
-
Oklahoma City, Oklahoma, Verenigde Staten, 73104
- University of Oklahoma Health Sciences Center
-
Oklahoma City, Oklahoma, Verenigde Staten, 73120
- Mercy Hospital Oklahoma City
-
Tulsa, Oklahoma, Verenigde Staten, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
-
-
Oregon
-
Baker City, Oregon, Verenigde Staten, 97814
- Saint Alphonsus Cancer Care Center-Baker City
-
Bend, Oregon, Verenigde Staten, 97701
- Saint Charles Health System
-
Clackamas, Oregon, Verenigde Staten, 97015
- Clackamas Radiation Oncology Center
-
Clackamas, Oregon, Verenigde Staten, 97015
- Providence Cancer Institute Clackamas Clinic
-
Coos Bay, Oregon, Verenigde Staten, 97420
- Bay Area Hospital
-
Newberg, Oregon, Verenigde Staten, 97132
- Providence Newberg Medical Center
-
Ontario, Oregon, Verenigde Staten, 97914
- Saint Alphonsus Cancer Care Center-Ontario
-
Oregon City, Oregon, Verenigde Staten, 97045
- Providence Willamette Falls Medical Center
-
Portland, Oregon, Verenigde Staten, 97213
- Providence Portland Medical Center
-
Portland, Oregon, Verenigde Staten, 97225
- Providence Saint Vincent Medical Center
-
Redmond, Oregon, Verenigde Staten, 97756
- Saint Charles Health System-Redmond
-
-
Pennsylvania
-
Hershey, Pennsylvania, Verenigde Staten, 17033-0850
- Penn State Milton S Hershey Medical Center
-
Philadelphia, Pennsylvania, Verenigde Staten, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, Verenigde Staten, 19104
- University of Pennsylvania/Abramson Cancer Center
-
-
South Carolina
-
Boiling Springs, South Carolina, Verenigde Staten, 29316
- Prisma Health Cancer Institute - Spartanburg
-
Columbia, South Carolina, Verenigde Staten, 29203
- Prisma Health Richland Hospital
-
Easley, South Carolina, Verenigde Staten, 29640
- Prisma Health Cancer Institute - Easley
-
Greenville, South Carolina, Verenigde Staten, 29605
- Prisma Health Cancer Institute - Faris
-
Greenville, South Carolina, Verenigde Staten, 29607
- Saint Francis Cancer Center
-
Greenville, South Carolina, Verenigde Staten, 29615
- Prisma Health Cancer Institute - Eastside
-
Greenville, South Carolina, Verenigde Staten, 29605
- Prisma Health Cancer Institute - Butternut
-
Greenville, South Carolina, Verenigde Staten, 29601
- Saint Francis Hospital
-
Greenville, South Carolina, Verenigde Staten, 29605
- BI-LO Charities Children's Cancer Center
-
Greenville, South Carolina, Verenigde Staten, 29605
- Prisma Health Greenville Memorial Hospital
-
Greer, South Carolina, Verenigde Staten, 29650
- Prisma Health Cancer Institute - Greer
-
Seneca, South Carolina, Verenigde Staten, 29672
- Prisma Health Cancer Institute - Seneca
-
-
Tennessee
-
Chattanooga, Tennessee, Verenigde Staten, 37404
- Memorial Hospital
-
Hixson, Tennessee, Verenigde Staten, 37343
- Pulmonary Medicine Center of Chattanooga-Hixson
-
Knoxville, Tennessee, Verenigde Staten, 37916
- East Tennessee Childrens Hospital
-
Memphis, Tennessee, Verenigde Staten, 38105
- Saint Jude Children's Research Hospital
-
Nashville, Tennessee, Verenigde Staten, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, Verenigde Staten, 37203
- The Children's Hospital at TriStar Centennial
-
Ooltewah, Tennessee, Verenigde Staten, 37363
- Memorial GYN Plus
-
-
Texas
-
Austin, Texas, Verenigde Staten, 78723
- Dell Children's Medical Center of Central Texas
-
Bryan, Texas, Verenigde Staten, 77802
- Saint Joseph Regional Cancer Center
-
Corpus Christi, Texas, Verenigde Staten, 78411
- Driscoll Children's Hospital
-
El Paso, Texas, Verenigde Staten, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, Verenigde Staten, 76104
- Cook Children's Medical Center
-
San Antonio, Texas, Verenigde Staten, 78207
- Children's Hospital of San Antonio
-
-
Utah
-
American Fork, Utah, Verenigde Staten, 84003
- American Fork Hospital / Huntsman Intermountain Cancer Center
-
Cedar City, Utah, Verenigde Staten, 84720
- Sandra L Maxwell Cancer Center
-
Logan, Utah, Verenigde Staten, 84321
- Logan Regional Hospital
-
Murray, Utah, Verenigde Staten, 84107
- Intermountain Medical Center
-
Ogden, Utah, Verenigde Staten, 84403
- McKay-Dee Hospital Center
-
Riverton, Utah, Verenigde Staten, 84065
- Riverton Hospital
-
Salt Lake City, Utah, Verenigde Staten, 84106
- Utah Cancer Specialists-Salt Lake City
-
Salt Lake City, Utah, Verenigde Staten, 84143
- LDS Hospital
-
St. George, Utah, Verenigde Staten, 84770
- Saint George Regional Medical Center
-
-
Virginia
-
Norfolk, Virginia, Verenigde Staten, 23507
- Children's Hospital of The King's Daughters
-
-
Washington
-
Aberdeen, Washington, Verenigde Staten, 98520
- Providence Regional Cancer System-Aberdeen
-
Auburn, Washington, Verenigde Staten, 98001
- MultiCare Auburn Medical Center
-
Bellevue, Washington, Verenigde Staten, 98004
- Overlake Medical Center
-
Bellingham, Washington, Verenigde Staten, 98225
- PeaceHealth Saint Joseph Medical Center
-
Burien, Washington, Verenigde Staten, 98166
- Saint Anne Hospital
-
Centralia, Washington, Verenigde Staten, 98531
- Providence Regional Cancer System-Centralia
-
Edmonds, Washington, Verenigde Staten, 98026
- Swedish Cancer Institute-Edmonds
-
Enumclaw, Washington, Verenigde Staten, 98022
- Saint Elizabeth Hospital
-
Everett, Washington, Verenigde Staten, 98201
- Providence Regional Cancer Partnership
-
Federal Way, Washington, Verenigde Staten, 98003
- Saint Francis Hospital
-
Gig Harbor, Washington, Verenigde Staten, 98335
- MultiCare Gig Harbor Medical Park
-
Issaquah, Washington, Verenigde Staten, 98029
- Swedish Cancer Institute-Issaquah
-
Kennewick, Washington, Verenigde Staten, 99336
- Kadlec Clinic Hematology and Oncology
-
Lacey, Washington, Verenigde Staten, 98503
- Providence Regional Cancer System-Lacey
-
Lakewood, Washington, Verenigde Staten, 98499
- Saint Clare Hospital
-
Longview, Washington, Verenigde Staten, 98632
- PeaceHealth Saint John Medical Center
-
Port Townsend, Washington, Verenigde Staten, 98368
- Jefferson Healthcare
-
Poulsbo, Washington, Verenigde Staten, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
-
Puyallup, Washington, Verenigde Staten, 98372
- MultiCare Good Samaritan Hospital
-
Renton, Washington, Verenigde Staten, 98055
- Valley Medical Center
-
Seattle, Washington, Verenigde Staten, 98105
- Seattle Children's Hospital
-
Seattle, Washington, Verenigde Staten, 98107
- Swedish Medical Center-Ballard Campus
-
Seattle, Washington, Verenigde Staten, 98122
- Swedish Medical Center-First Hill
-
Seattle, Washington, Verenigde Staten, 98112
- Kaiser Permanente Washington
-
Seattle, Washington, Verenigde Staten, 98104
- Pacific Gynecology Specialists
-
Seattle, Washington, Verenigde Staten, 98122-5711
- Swedish Medical Center-Cherry Hill
-
Sedro-Woolley, Washington, Verenigde Staten, 98284
- PeaceHealth United General Medical Center
-
Shelton, Washington, Verenigde Staten, 98584
- Providence Regional Cancer System-Shelton
-
Silverdale, Washington, Verenigde Staten, 98383
- Saint Joseph Medical Center Hematology and Oncology - Silverdale
-
Spokane, Washington, Verenigde Staten, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Spokane, Washington, Verenigde Staten, 99204
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
-
Spokane, Washington, Verenigde Staten, 99218
- MultiCare Deaconess Cancer and Blood Specialty Center - North
-
Spokane Valley, Washington, Verenigde Staten, 99216
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
-
Tacoma, Washington, Verenigde Staten, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, Verenigde Staten, 98405
- Northwest Medical Specialties PLLC
-
Tacoma, Washington, Verenigde Staten, 98431
- Madigan Army Medical Center
-
Tacoma, Washington, Verenigde Staten, 98405
- MultiCare Tacoma General Hospital
-
Tacoma, Washington, Verenigde Staten, 98405
- Franciscan Research Center-Northwest Medical Plaza
-
Vancouver, Washington, Verenigde Staten, 98664
- PeaceHealth Southwest Medical Center
-
Walla Walla, Washington, Verenigde Staten, 99362
- Providence Saint Mary Regional Cancer Center
-
Yakima, Washington, Verenigde Staten, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
-
Yelm, Washington, Verenigde Staten, 98597
- Providence Regional Cancer System-Yelm
-
-
West Virginia
-
Bridgeport, West Virginia, Verenigde Staten, 26330
- United Hospital Center
-
Martinsburg, West Virginia, Verenigde Staten, 25401
- WVUH-Berkely Medical Center
-
Morgantown, West Virginia, Verenigde Staten, 26506
- West Virginia University Healthcare
-
Parkersburg, West Virginia, Verenigde Staten, 26101
- Camden Clark Medical Center
-
-
Wisconsin
-
Ashland, Wisconsin, Verenigde Staten, 54806
- Duluth Clinic Ashland
-
Ashland, Wisconsin, Verenigde Staten, 54806
- Northwest Wisconsin Cancer Center
-
Burlington, Wisconsin, Verenigde Staten, 53105
- Aurora Cancer Care-Southern Lakes VLCC
-
Chippewa Falls, Wisconsin, Verenigde Staten, 54729
- Marshfield Clinic-Chippewa Center
-
Eau Claire, Wisconsin, Verenigde Staten, 54701
- Marshfield Medical Center-EC Cancer Center
-
Fond du Lac, Wisconsin, Verenigde Staten, 54937
- Aurora Health Center-Fond du Lac
-
Germantown, Wisconsin, Verenigde Staten, 53022
- Aurora Health Care Germantown Health Center
-
Grafton, Wisconsin, Verenigde Staten, 53024
- Aurora Cancer Care-Grafton
-
Green Bay, Wisconsin, Verenigde Staten, 54311
- Aurora BayCare Medical Center
-
Kenosha, Wisconsin, Verenigde Staten, 53142
- Aurora Cancer Care-Kenosha South
-
La Crosse, Wisconsin, Verenigde Staten, 54601
- Gundersen Lutheran Medical Center
-
Ladysmith, Wisconsin, Verenigde Staten, 54848
- Marshfield Medical Center - Ladysmith
-
Madison, Wisconsin, Verenigde Staten, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marinette, Wisconsin, Verenigde Staten, 54143
- Aurora Bay Area Medical Group-Marinette
-
Marshfield, Wisconsin, Verenigde Staten, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, Verenigde Staten, 53226
- Medical College of Wisconsin
-
Milwaukee, Wisconsin, Verenigde Staten, 53209
- Aurora Cancer Care-Milwaukee
-
Milwaukee, Wisconsin, Verenigde Staten, 53215
- Aurora Saint Luke's Medical Center
-
Milwaukee, Wisconsin, Verenigde Staten, 53233
- Aurora Sinai Medical Center
-
Minocqua, Wisconsin, Verenigde Staten, 54548
- Marshfield Medical Center - Minocqua
-
Oshkosh, Wisconsin, Verenigde Staten, 54904
- Vince Lombardi Cancer Clinic - Oshkosh
-
Racine, Wisconsin, Verenigde Staten, 53406
- Aurora Cancer Care-Racine
-
Rice Lake, Wisconsin, Verenigde Staten, 54868
- Marshfield Medical Center-Rice Lake
-
Sheboygan, Wisconsin, Verenigde Staten, 53081
- Vince Lombardi Cancer Clinic-Sheboygan
-
Stevens Point, Wisconsin, Verenigde Staten, 54482
- Marshfield Medical Center-River Region at Stevens Point
-
Summit, Wisconsin, Verenigde Staten, 53066
- Aurora Medical Center in Summit
-
Two Rivers, Wisconsin, Verenigde Staten, 54241
- Vince Lombardi Cancer Clinic-Two Rivers
-
Wausau, Wisconsin, Verenigde Staten, 54401
- Marshfield Clinic-Wausau Center
-
Wauwatosa, Wisconsin, Verenigde Staten, 53226
- Aurora Cancer Care-Milwaukee West
-
West Allis, Wisconsin, Verenigde Staten, 53227
- Aurora West Allis Medical Center
-
Weston, Wisconsin, Verenigde Staten, 54476
- Marshfield Medical Center - Weston
-
Wisconsin Rapids, Wisconsin, Verenigde Staten, 54494
- Marshfield Clinic - Wisconsin Rapids Center
-
-
Wyoming
-
Cheyenne, Wyoming, Verenigde Staten, 82001
- Cheyenne Regional Medical Center-West
-
Cody, Wyoming, Verenigde Staten, 82414
- Billings Clinic-Cody
-
Sheridan, Wyoming, Verenigde Staten, 82801
- Welch Cancer Center
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
-
PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
-
Age >= 18 years
-
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
-
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
-
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
-
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)
-
Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
-
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
-
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
-
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
-
Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10^9/L) (obtained within 2 weeks prior to registration)
-
Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
-
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)
-
Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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
Andere namen:
Undergo CT
Andere namen:
Undergo biopsy
Andere namen:
Undergo collection of blood
Andere namen:
Given IV
Andere namen:
Undergo PET
Andere namen:
|
|
Experimenteel: 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
Andere namen:
Undergo biopsy
Andere namen:
Undergo collection of blood
Andere namen:
Given IV
Andere namen:
Undergo PET
Andere namen:
Given IV
Andere namen:
|
|
Experimenteel: 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
Andere namen:
Undergo CT
Andere namen:
Undergo biopsy
Andere namen:
Undergo collection of blood
Andere namen:
Given IV
Andere namen:
Undergo PET
Andere namen:
Given IV
Andere namen:
|
|
Experimenteel: 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
Andere namen:
Undergo biopsy
Andere namen:
Undergo collection of blood
Andere namen:
Given IV
Andere namen:
Undergo PET
Andere namen:
Given IV
Andere namen:
|
|
Experimenteel: 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
Andere namen:
Undergo CT
Andere namen:
Undergo biopsy
Andere namen:
Undergo collection of blood
Andere namen:
Given IV
Andere namen:
Undergo PET
Andere namen:
Given IV
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Maximum tolerated dose (MTD) of each combination (Phase I)
Tijdsspanne: 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)
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Complete response (CR) rate (Phase I)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Effecten van combinaties op systemische immuniteit (Fase I en II)
Tijdsspanne: Baseline tot maximaal 6 weken na voltooiing van de studiebehandeling
|
Baseline tot maximaal 6 weken na voltooiing van de studiebehandeling
|
|
|
Change in the percentage of activated T cells and natural killer cells (Phase I and II)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: Completion of study treatment
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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
|
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Absolute maximum standard uptake value (SUVmax) (Phase II)
Tijdsspanne: Up to cycle 10
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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
|
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Metabolic whole body tumor volume (MTV) and tumor lesion glycolysis (TLG)
Tijdsspanne: 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
|
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Percent change in SUVmax, MTV and TLG between baseline and during therapy
Tijdsspanne: 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
|
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Percent change in size (sum of perpendicular diameters [SPD]) on computed tomography (CT)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Catherine S Diefenbach, ECOG-ACRIN Cancer Research Group
Publicaties en nuttige links
Algemene publicaties
- 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.
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Geschat)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Peptiden
- Aminozuren, peptiden en eiwitten
- Oligopeptiden
- Eiwitten
- Onderzoekstechnieken
- Klinische laboratoriumtechnieken
- Diagnostische technieken en procedures
- Diagnose
- Chirurgische procedures, operatief
- Cytologische technieken
- Cytodiagnose
- Biologische factoren
- Antilichamen, monoklonaal, gehumaniseerd
- Antilichamen, monoklonaal
- Antilichamen
- Immunoglobulinen
- Immunoproteïnen
- Bloedeiwitten
- Serum -globulines
- Globulines
- Diagnostische technieken, chirurgisch
- Chemie -technieken, analytisch
- Spectrumanalyse
- Receptoren, celoppervlak
- Membraaneiwitten
- Antigenen
- Antigenen, oppervlak
- Biomarkers
- Receptoren, immunologisch
- Antigenen, differentiatie, T-lymfocyt
- Antigenen, differentiatie
- Immuun checkpoint -eiwitten
- Costimulatoire en remmende T-celreceptoren
- Nivolumab
- Ipilimumab
- Brentuximab Vedotin
- Biopsie
- Exemplaarbehandeling
- Magnetische resonantiespectroscopie
- CTLA-4 antigeen
Andere studie-ID-nummers
- NCI-2013-01275
- U10CA180820 (Subsidie/contract van de Amerikaanse NIH)
- U24CA196172 (Subsidie/contract van de Amerikaanse NIH)
- NCI-2013-01275 (Register-ID: CTRP (Clinical Trial Reporting Program))
- E4412 (Andere identificatie: CTEP)
- S14-00011
- E4412
- E4412 (Andere identificatie: ECOG-ACRIN Cancer Research Group)
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