Brentuximab Vedotin et Nivolumab avec ou sans ipilimumab dans le traitement de patients atteints d'un lymphome de Hodgkin récidivant ou réfractaire
Une étude de phase I avec une cohorte d'expansion/étude de phase II randomisée des combinaisons d'ipilimumab, de nivolumab et de brentuximab védotine chez des patients atteints d'un lymphome de Hodgkin récidivant/réfractaire
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.
Aperçu de l'étude
Statut
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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Alabama
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Birmingham, Alabama, États-Unis, 35233
- University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, États-Unis, 35233
- Children's Hospital of Alabama
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Alaska
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Anchorage, Alaska, États-Unis, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, États-Unis, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, États-Unis, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, États-Unis, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, États-Unis, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, États-Unis, 99508
- Katmai Oncology Group
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Anchorage, Alaska, États-Unis, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, États-Unis, 99504
- Anchorage Radiation Therapy Center
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Fairbanks, Alaska, États-Unis, 99701
- Fairbanks Memorial Hospital
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Arizona
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Kingman, Arizona, États-Unis, 86401
- Kingman Regional Medical Center
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Phoenix, Arizona, États-Unis, 85004
- Cancer Center at Saint Joseph's
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Arkansas
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Fort Smith, Arkansas, États-Unis, 72903
- Mercy Hospital Fort Smith
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Hot Springs, Arkansas, États-Unis, 71913
- CHI Saint Vincent Cancer Center Hot Springs
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California
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Antioch, California, États-Unis, 94531
- Kaiser Permanente-Deer Valley Medical Center
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Arroyo Grande, California, États-Unis, 93420
- PCR Oncology
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Arroyo Grande, California, États-Unis, 93420
- Mission Hope Medical Oncology - Arroyo Grande
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Burbank, California, États-Unis, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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Dublin, California, États-Unis, 94568
- Kaiser Permanente Dublin
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Fremont, California, États-Unis, 94538
- Kaiser Permanente-Fremont
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Fresno, California, États-Unis, 93720
- Kaiser Permanente-Fresno
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Fresno, California, États-Unis, 93720
- Fresno Cancer Center
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Modesto, California, États-Unis, 95356
- Kaiser Permanente-Modesto
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Oakland, California, États-Unis, 94611
- Kaiser Permanente-Oakland
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Oakland, California, États-Unis, 94611
- Kaiser Permanente Oakland-Broadway
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Orange, California, États-Unis, 92868
- Children's Hospital of Orange County
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Palo Alto, California, États-Unis, 94304
- Stanford Cancer Institute Palo Alto
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Rancho Cordova, California, États-Unis, 95670
- Kaiser Permanente-Rancho Cordova Cancer Center
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Redwood City, California, États-Unis, 94063
- Kaiser Permanente-Redwood City
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Richmond, California, États-Unis, 94801
- Kaiser Permanente-Richmond
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Rohnert Park, California, États-Unis, 94928
- Rohnert Park Cancer Center
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Roseville, California, États-Unis, 95678
- The Permanente Medical Group-Roseville Radiation Oncology
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Roseville, California, États-Unis, 95661
- Kaiser Permanente-Roseville
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Sacramento, California, États-Unis, 95814
- Kaiser Permanente Downtown Commons
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Sacramento, California, États-Unis, 95823
- Kaiser Permanente-South Sacramento
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Sacramento, California, États-Unis, 95823
- South Sacramento Cancer Center
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Sacramento, California, États-Unis, 95825
- Kaiser Permanente Sacramento Medical Center
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San Francisco, California, États-Unis, 94115
- Kaiser Permanente-San Francisco
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San Francisco, California, États-Unis, 94158
- UCSF Medical Center-Mission Bay
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San Jose, California, États-Unis, 95119
- Kaiser Permanente-Santa Teresa-San Jose
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San Leandro, California, États-Unis, 94577
- Kaiser Permanente San Leandro
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San Luis Obispo, California, États-Unis, 93401
- Pacific Central Coast Health Center-San Luis Obispo
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San Rafael, California, États-Unis, 94903
- Kaiser San Rafael-Gallinas
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San Rafael, California, États-Unis, 94903
- Kaiser Permanente-San Rafael
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Santa Clara, California, États-Unis, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Maria, California, États-Unis, 93444
- Mission Hope Medical Oncology - Santa Maria
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Santa Rosa, California, États-Unis, 95403
- Kaiser Permanente-Santa Rosa
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South San Francisco, California, États-Unis, 94080
- Kaiser Permanente Cancer Treatment Center
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South San Francisco, California, États-Unis, 94080
- Kaiser Permanente-South San Francisco
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Stockton, California, États-Unis, 95210
- Kaiser Permanente-Stockton
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Vacaville, California, États-Unis, 95688
- Kaiser Permanente Medical Center-Vacaville
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Vallejo, California, États-Unis, 94589
- Kaiser Permanente-Vallejo
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Walnut Creek, California, États-Unis, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, États-Unis, 80012
- Rocky Mountain Cancer Centers-Aurora
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Aurora, Colorado, États-Unis, 80012
- The Medical Center of Aurora
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Boulder, Colorado, États-Unis, 80303
- Boulder Community Foothills Hospital
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Boulder, Colorado, États-Unis, 80304
- Rocky Mountain Cancer Centers-Boulder
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Centennial, Colorado, États-Unis, 80112
- Rocky Mountain Cancer Centers - Centennial
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Colorado Springs, Colorado, États-Unis, 80907
- Penrose-Saint Francis Healthcare
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Colorado Springs, Colorado, États-Unis, 80907
- Rocky Mountain Cancer Centers-Penrose
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Denver, Colorado, États-Unis, 80218
- Presbyterian - Saint Lukes Medical Center - Health One
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Denver, Colorado, États-Unis, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Denver, Colorado, États-Unis, 80220
- Rose Medical Center
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Denver, Colorado, États-Unis, 80218
- Rocky Mountain Cancer Centers-Midtown
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Denver, Colorado, États-Unis, 80220
- Rocky Mountain Cancer Centers-Rose
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Denver, Colorado, États-Unis, 80204
- Denver Health Medical Center
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Denver, Colorado, États-Unis, 80218
- Colorado Blood Cancer Institute
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Denver, Colorado, États-Unis, 80204
- Cancer Center of Colorado at Sloan's Lake
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Denver, Colorado, États-Unis, 80209
- The Women's Imaging Center
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Denver, Colorado, États-Unis, 80206
- National Jewish Health-Main Campus
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Denver, Colorado, États-Unis, 80220
- Western Surgical Care
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Denver, Colorado, États-Unis, 80218
- Saint Joseph Hospital - Cancer Centers of Colorado
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Denver, Colorado, États-Unis, 80210
- AdventHealth Porter
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Durango, Colorado, États-Unis, 81301
- Mercy Medical Center
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Durango, Colorado, États-Unis, 81301
- CommonSpirit Cancer Center Mercy
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Englewood, Colorado, États-Unis, 80113
- Mountain Blue Cancer Care Center - Swedish
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Englewood, Colorado, États-Unis, 80113
- Swedish Medical Center
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Englewood, Colorado, États-Unis, 80113
- Rocky Mountain Cancer Centers - Swedish
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Golden, Colorado, États-Unis, 80401
- Mountain Blue Cancer Care Center
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Golden, Colorado, États-Unis, 80401
- National Jewish Health-Western Hematology Oncology
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Grand Junction, Colorado, États-Unis, 81501
- Saint Mary's Hospital and Regional Medical Center
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Greeley, Colorado, États-Unis, 80631
- Banner North Colorado Medical Center
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Lafayette, Colorado, États-Unis, 80026
- Good Samaritan Hospital - Cancer Centers of Colorado
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Lakewood, Colorado, États-Unis, 80228
- Rocky Mountain Cancer Centers-Lakewood
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Lakewood, Colorado, États-Unis, 80228
- CommonSpirit Saint Anthony Hospital Cancer Center
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Littleton, Colorado, États-Unis, 80120
- Rocky Mountain Cancer Centers-Littleton
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Littleton, Colorado, États-Unis, 80122
- AdventHealth Littleton
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Lone Tree, Colorado, États-Unis, 80124
- Sky Ridge Medical Center
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Lone Tree, Colorado, États-Unis, 80124
- Rocky Mountain Cancer Centers-Sky Ridge
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Longmont, Colorado, États-Unis, 80501
- Longmont United Hospital
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Longmont, Colorado, États-Unis, 80501
- Rocky Mountain Cancer Centers-Longmont
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Loveland, Colorado, États-Unis, 80539
- Banner North Colorado Medical Center - Loveland Campus
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Parker, Colorado, États-Unis, 80138
- Rocky Mountain Cancer Centers-Parker
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Parker, Colorado, États-Unis, 80138
- AdventHealth Parker
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Pueblo, Colorado, États-Unis, 81008
- Rocky Mountain Cancer Centers - Pueblo
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Thornton, Colorado, États-Unis, 80260
- Rocky Mountain Cancer Centers-Thornton
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Thornton, Colorado, États-Unis, 80260
- National Jewish Health-Northern Hematology Oncology
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Wheat Ridge, Colorado, États-Unis, 80401
- Intermountain Health Lutheran Hospital
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District of Columbia
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Washington D.C., District of Columbia, États-Unis, 20010
- Children's National Medical Center
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Florida
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Fort Myers, Florida, États-Unis, 33905
- Regional Cancer Center-Lee Memorial Health System
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Fort Myers, Florida, États-Unis, 33908
- Golisano Children's Hospital of Southwest Florida
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St. Petersburg, Florida, États-Unis, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, États-Unis, 33606
- Tampa General Hospital
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Tampa, Florida, États-Unis, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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Georgia
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Atlanta, Georgia, États-Unis, 30322
- Emory University Hospital/Winship Cancer Institute
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Atlanta, Georgia, États-Unis, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
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Hawaii
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Honolulu, Hawaii, États-Unis, 96819
- Kaiser Permanente Moanalua Medical Center
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Idaho
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Boise, Idaho, États-Unis, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, États-Unis, 83712
- Saint Luke's Cancer Institute - Boise
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Caldwell, Idaho, États-Unis, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, États-Unis, 83814
- Kootenai Health - Coeur d'Alene
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Emmett, Idaho, États-Unis, 83617
- Walter Knox Memorial Hospital
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Fruitland, Idaho, États-Unis, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, États-Unis, 83642
- Idaho Urologic Institute-Meridian
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Meridian, Idaho, États-Unis, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, États-Unis, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Nampa, Idaho, États-Unis, 83687
- Saint Luke's Cancer Institute - Nampa
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Post Falls, Idaho, États-Unis, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, États-Unis, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Twin Falls, Idaho, États-Unis, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Alton, Illinois, États-Unis, 62002
- OSF Saint Anthony's Health Center
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Aurora, Illinois, États-Unis, 60504
- Rush-Copley Medical Center
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Bloomington, Illinois, États-Unis, 61704
- Illinois CancerCare-Bloomington
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Canton, Illinois, États-Unis, 61520
- Illinois CancerCare-Canton
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Carbondale, Illinois, États-Unis, 62902
- Memorial Hospital of Carbondale
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Carterville, Illinois, États-Unis, 62918
- SIH Cancer Institute
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Carthage, Illinois, États-Unis, 62321
- Illinois CancerCare-Carthage
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Centralia, Illinois, États-Unis, 62801
- Centralia Oncology Clinic
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Chicago, Illinois, États-Unis, 60611
- Northwestern University
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Chicago, Illinois, États-Unis, 60612
- University of Illinois
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Chicago, Illinois, États-Unis, 60612
- Rush MD Anderson Cancer Center
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Danville, Illinois, États-Unis, 61832
- Carle at The Riverfront
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Decatur, Illinois, États-Unis, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, États-Unis, 62526
- Cancer Care Specialists of Illinois - Decatur
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Dixon, Illinois, États-Unis, 61021
- Illinois CancerCare-Dixon
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Effingham, Illinois, États-Unis, 62401
- Crossroads Cancer Center
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Effingham, Illinois, États-Unis, 62401
- Carle Physician Group-Effingham
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Eureka, Illinois, États-Unis, 61530
- Illinois CancerCare-Eureka
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Galesburg, Illinois, États-Unis, 61401
- Western Illinois Cancer Treatment Center
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Galesburg, Illinois, États-Unis, 61401
- Illinois CancerCare-Galesburg
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Joliet, Illinois, États-Unis, 60435
- Duly Health and Care Joliet
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Kewanee, Illinois, États-Unis, 61443
- Illinois CancerCare-Kewanee Clinic
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Macomb, Illinois, États-Unis, 61455
- Illinois CancerCare-Macomb
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Mattoon, Illinois, États-Unis, 61938
- Carle Physician Group-Mattoon/Charleston
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Mount Vernon, Illinois, États-Unis, 62864
- SSM Health Good Samaritan
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O'Fallon, Illinois, États-Unis, 62269
- Cancer Care Center of O'Fallon
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Ottawa, Illinois, États-Unis, 61350
- Illinois CancerCare-Ottawa Clinic
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Pekin, Illinois, États-Unis, 61554
- Illinois CancerCare-Pekin
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Peoria, Illinois, États-Unis, 61636
- Methodist Medical Center of Illinois
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Peoria, Illinois, États-Unis, 61615
- Illinois CancerCare-Peoria
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Peru, Illinois, États-Unis, 61354
- Illinois CancerCare-Peru
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Peru, Illinois, États-Unis, 61354
- Valley Radiation Oncology
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Princeton, Illinois, États-Unis, 61356
- Illinois CancerCare-Princeton
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Springfield, Illinois, États-Unis, 62702
- Southern Illinois University School of Medicine
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Springfield, Illinois, États-Unis, 62702
- Springfield Clinic
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Springfield, Illinois, États-Unis, 62781
- Springfield Memorial Hospital
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Swansea, Illinois, États-Unis, 62226
- Southwest Illinois Health Services LLP
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Urbana, Illinois, États-Unis, 61801
- Carle Cancer Center
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Urbana, Illinois, États-Unis, 61801
- The Carle Foundation Hospital
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Washington, Illinois, États-Unis, 61571
- Illinois CancerCare - Washington
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Yorkville, Illinois, États-Unis, 60560
- Rush-Copley Healthcare Center
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Indiana
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Evansville, Indiana, États-Unis, 47713
- Deaconess Clinic Downtown
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Indianapolis, Indiana, États-Unis, 46202
- Indiana University/Melvin and Bren Simon Cancer Center
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Newburgh, Indiana, États-Unis, 47630
- Chancellor Center for Oncology
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Iowa
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Clive, Iowa, États-Unis, 50325
- Mercy Cancer Center-West Lakes
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Clive, Iowa, États-Unis, 50325
- UI Health Care Mission Cancer and Blood - West Des Moines Clinic
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Council Bluffs, Iowa, États-Unis, 51503
- Alegent Health Mercy Hospital
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Creston, Iowa, États-Unis, 50801
- Greater Regional Medical Center
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Des Moines, Iowa, États-Unis, 50314
- Mercy Medical Center - Des Moines
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Des Moines, Iowa, États-Unis, 50314
- UI Health Care Mission Cancer and Blood - Laurel Clinic
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West Des Moines, Iowa, États-Unis, 50266
- Mercy Medical Center-West Lakes
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Kansas
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Garden City, Kansas, États-Unis, 67846
- Central Care Cancer Center - Garden City
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Great Bend, Kansas, États-Unis, 67530
- Central Care Cancer Center - Great Bend
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Kentucky
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Bardstown, Kentucky, États-Unis, 40004
- CommonSpirit Saint Joseph Hospital - Bardstown
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Corbin, Kentucky, États-Unis, 40701
- Commonwealth Cancer Center-Corbin
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Lexington, Kentucky, États-Unis, 40504
- Saint Joseph Radiation Oncology Resource Center
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Lexington, Kentucky, États-Unis, 40509
- CommonSpirit Saint Joseph Medical Center - East Lexington
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London, Kentucky, États-Unis, 40741
- CommonSpirit Saint Joseph Hospital London
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Louisville, Kentucky, États-Unis, 40202
- Jewish Hospital
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Louisville, Kentucky, États-Unis, 40245
- UofL Health Medical Center Northeast
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Louisville, Kentucky, États-Unis, 40215
- Saints Mary and Elizabeth Hospital
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Paducah, Kentucky, États-Unis, 42003
- Mercy Health - Paducah Cancer Center
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Shepherdsville, Kentucky, États-Unis, 40165
- Jewish Hospital Medical Center South
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Louisiana
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Baton Rouge, Louisiana, États-Unis, 70805
- LSU Health Baton Rouge-North Clinic
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Baton Rouge, Louisiana, États-Unis, 70809
- Louisiana Hematology Oncology Associates LLC
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Baton Rouge, Louisiana, États-Unis, 70809
- Mary Bird Perkins Cancer Center
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Baton Rouge, Louisiana, États-Unis, 70808
- Our Lady of The Lake
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Baton Rouge, Louisiana, États-Unis, 70808
- Our Lady of the Lake Physician Group
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Covington, Louisiana, États-Unis, 70433
- Northshore Oncology Associates-Covington
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Houma, Louisiana, États-Unis, 70360
- Terrebonne General Medical Center
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Houma, Louisiana, États-Unis, 70360
- Oncology Center of The South Incorporated
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Maryland
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Baltimore, Maryland, États-Unis, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, États-Unis, 21229
- Saint Agnes Hospital
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Bethesda, Maryland, États-Unis, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, États-Unis, 02111
- Tufts Medical Center
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Michigan
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Port Huron, Michigan, États-Unis, 48060
- Lake Huron Medical Center
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Port Huron, Michigan, États-Unis, 48060
- Huron Medical Center PC
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Minnesota
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Aitkin, Minnesota, États-Unis, 56431
- Riverwood Healthcare Center
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Brainerd, Minnesota, États-Unis, 56401
- Essentia Health Saint Joseph's Medical Center
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Deer River, Minnesota, États-Unis, 56636
- Essentia Health - Deer River Clinic
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Detroit Lakes, Minnesota, États-Unis, 56501
- Essentia Health Saint Mary's - Detroit Lakes Clinic
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Duluth, Minnesota, États-Unis, 55805
- Essentia Health Cancer Center
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Duluth, Minnesota, États-Unis, 55805
- Essentia Health Saint Mary's Medical Center
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Duluth, Minnesota, États-Unis, 55805
- Miller-Dwan Hospital
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Fergus Falls, Minnesota, États-Unis, 56537
- Lake Region Healthcare Corporation-Cancer Care
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Fosston, Minnesota, États-Unis, 56542
- Essentia Health - Fosston
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Hibbing, Minnesota, États-Unis, 55746
- Essentia Health Hibbing Clinic
-
Park Rapids, Minnesota, États-Unis, 56470
- Essentia Health - Park Rapids
-
Rochester, Minnesota, États-Unis, 55905
- Mayo Clinic in Rochester
-
Sandstone, Minnesota, États-Unis, 55072
- Essentia Health Sandstone
-
Virginia, Minnesota, États-Unis, 55792
- Essentia Health Virginia Clinic
-
-
Missouri
-
Ballwin, Missouri, États-Unis, 63011
- Mercy Oncology and Hematology - Clayton-Clarkson
-
Bolivar, Missouri, États-Unis, 65613
- Central Care Cancer Center - Bolivar
-
Bonne Terre, Missouri, États-Unis, 63628
- Parkland Health Center-Bonne Terre
-
Branson, Missouri, États-Unis, 65616
- Cox Cancer Center Branson
-
Cape Girardeau, Missouri, États-Unis, 63703
- Saint Francis Medical Center
-
Cape Girardeau, Missouri, États-Unis, 63703
- Mercy Cancer Center - Cape Girardeau
-
Chesterfield, Missouri, États-Unis, 63017
- Saint Luke's Hospital
-
City of Saint Peters, Missouri, États-Unis, 63376
- Siteman Cancer Center at Saint Peters Hospital
-
Creve Coeur, Missouri, États-Unis, 63141
- Siteman Cancer Center at West County Hospital
-
Farmington, Missouri, États-Unis, 63640
- Parkland Health Center - Farmington
-
Jefferson City, Missouri, États-Unis, 65109
- MU Health Care Goldschmidt Cancer Center
-
Joplin, Missouri, États-Unis, 64804
- Freeman Health System
-
Joplin, Missouri, États-Unis, 64804
- Mercy Hospital Joplin
-
Kansas City, Missouri, États-Unis, 64108
- Children's Mercy Hospitals and Clinics
-
Rolla, Missouri, États-Unis, 65401
- Mercy Clinic-Rolla-Cancer and Hematology
-
Rolla, Missouri, États-Unis, 65401
- Phelps Health Delbert Day Cancer Institute
-
Saint Joseph, Missouri, États-Unis, 64506
- Heartland Regional Medical Center
-
Sainte Genevieve, Missouri, États-Unis, 63670
- Sainte Genevieve County Memorial Hospital
-
Springfield, Missouri, États-Unis, 65807
- CoxHealth South Hospital
-
Springfield, Missouri, États-Unis, 65804
- Mercy Hospital Springfield
-
St Louis, Missouri, États-Unis, 63110
- Washington University School of Medicine
-
St Louis, Missouri, États-Unis, 63129
- Siteman Cancer Center-South County
-
St Louis, Missouri, États-Unis, 63136
- Siteman Cancer Center at Christian Hospital
-
St Louis, Missouri, États-Unis, 63131
- Missouri Baptist Medical Center
-
St Louis, Missouri, États-Unis, 63109
- Mercy Infusion Center - Chippewa
-
St Louis, Missouri, États-Unis, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, États-Unis, 63128
- Mercy Hospital South
-
Sullivan, Missouri, États-Unis, 63080
- Missouri Baptist Sullivan Hospital
-
Washington, Missouri, États-Unis, 63090
- Mercy Hospital Washington
-
-
Montana
-
Anaconda, Montana, États-Unis, 59711
- Community Hospital of Anaconda
-
Billings, Montana, États-Unis, 59101
- Billings Clinic Cancer Center
-
Billings, Montana, États-Unis, 59101
- Saint Vincent Healthcare
-
Billings, Montana, États-Unis, 59102
- Saint Vincent Frontier Cancer Center
-
Bozeman, Montana, États-Unis, 59715
- Bozeman Health Deaconess Hospital
-
Butte, Montana, États-Unis, 59701
- Saint James Community Hospital and Cancer Treatment Center
-
Great Falls, Montana, États-Unis, 59405
- Great Falls Clinic
-
Great Falls, Montana, États-Unis, 59405
- Benefis Sletten Cancer Institute
-
Helena, Montana, États-Unis, 59601
- Saint Peter's Community Hospital
-
Kalispell, Montana, États-Unis, 59901
- Logan Health Medical Center
-
Missoula, Montana, États-Unis, 59802
- Saint Patrick Hospital - Community Hospital
-
Missoula, Montana, États-Unis, 59804
- Community Medical Center
-
-
Nebraska
-
Grand Island, Nebraska, États-Unis, 68803
- Nebraska Cancer Specialists/Oncology Hematology West PC
-
Kearney, Nebraska, États-Unis, 68847
- CHI Health Good Samaritan
-
Kearney, Nebraska, États-Unis, 68845
- Fred and Pamela Buffett Cancer Center - Kearney
-
Lincoln, Nebraska, États-Unis, 68510
- Saint Elizabeth Regional Medical Center
-
Omaha, Nebraska, États-Unis, 68124
- Alegent Health Bergan Mercy Medical Center
-
Omaha, Nebraska, États-Unis, 68122
- Alegent Health Immanuel Medical Center
-
Omaha, Nebraska, États-Unis, 68130
- Alegent Health Lakeside Hospital
-
Omaha, Nebraska, États-Unis, 68122
- Hematology and Oncology Consultants PC
-
Papillion, Nebraska, États-Unis, 68046
- Midlands Community Hospital
-
-
Nevada
-
Carson City, Nevada, États-Unis, 89703
- Carson Tahoe Regional Medical Center
-
Henderson, Nevada, États-Unis, 89052
- Comprehensive Cancer Centers of Nevada - Henderson
-
Henderson, Nevada, États-Unis, 89052
- Cancer and Blood Specialists-Henderson
-
Henderson, Nevada, États-Unis, 89052
- Las Vegas Cancer Center-Henderson
-
Henderson, Nevada, États-Unis, 89074
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
-
Henderson, Nevada, États-Unis, 89052
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
-
Henderson, Nevada, États-Unis, 89074
- Las Vegas Urology - Green Valley
-
Henderson, Nevada, États-Unis, 89074
- Las Vegas Urology - Pebble
-
Henderson, Nevada, États-Unis, 89074
- Urology Specialists of Nevada - Green Valley
-
Henderson, Nevada, États-Unis, 89074
- Oncology Las Vegas - Henderson
-
Las Vegas, Nevada, États-Unis, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, États-Unis, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, États-Unis, 89102
- OptumCare Cancer Care at Charleston
-
Las Vegas, Nevada, États-Unis, 89106
- Radiation Oncology Centers of Nevada Central
-
Las Vegas, Nevada, États-Unis, 89119
- Radiation Oncology Centers of Nevada Southeast
-
Las Vegas, Nevada, États-Unis, 89128
- Comprehensive Cancer Centers of Nevada - Northwest
-
Las Vegas, Nevada, États-Unis, 89128
- OptumCare Cancer Care at MountainView
-
Las Vegas, Nevada, États-Unis, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, États-Unis, 89144
- Comprehensive Cancer Centers of Nevada - Town Center
-
Las Vegas, Nevada, États-Unis, 89144
- Comprehensive Cancer Centers of Nevada-Summerlin
-
Las Vegas, Nevada, États-Unis, 89148
- Comprehensive Cancer Centers of Nevada
-
Las Vegas, Nevada, États-Unis, 89169
- Comprehensive Cancer Centers of Nevada - Central Valley
-
Las Vegas, Nevada, États-Unis, 89102
- University Medical Center of Southern Nevada
-
Las Vegas, Nevada, États-Unis, 89106
- Cancer and Blood Specialists-Shadow
-
Las Vegas, Nevada, États-Unis, 89109
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
-
Las Vegas, Nevada, États-Unis, 89113
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
-
Las Vegas, Nevada, États-Unis, 89128
- Cancer and Blood Specialists-Tenaya
-
Las Vegas, Nevada, États-Unis, 89128
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
-
Las Vegas, Nevada, États-Unis, 89148-2405
- Las Vegas Cancer Center-Medical Center
-
Las Vegas, Nevada, États-Unis, 89149
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
-
Las Vegas, Nevada, États-Unis, 89128
- Ann M Wierman MD LTD
-
Las Vegas, Nevada, États-Unis, 89074
- Las Vegas Urology - Pecos
-
Las Vegas, Nevada, États-Unis, 89102
- Desert West Surgery
-
Las Vegas, Nevada, États-Unis, 89103
- Hope Cancer Care of Nevada
-
Las Vegas, Nevada, États-Unis, 89106
- Urology Specialists of Nevada - Central
-
Las Vegas, Nevada, États-Unis, 89113
- Las Vegas Prostate Cancer Center
-
Las Vegas, Nevada, États-Unis, 89113
- Las Vegas Urology - Sunset
-
Las Vegas, Nevada, États-Unis, 89128
- Las Vegas Urology - Cathedral Rock
-
Las Vegas, Nevada, États-Unis, 89128
- Las Vegas Urology - Smoke Ranch
-
Las Vegas, Nevada, États-Unis, 89128
- Urology Specialists of Nevada - Northwest
-
Las Vegas, Nevada, États-Unis, 89169
- University Cancer Center
-
Las Vegas, Nevada, États-Unis, 89113
- Urology Specialists of Nevada - Southwest
-
Las Vegas, Nevada, États-Unis, 89128
- Oncology Las Vegas - Tenaya
-
Las Vegas, Nevada, États-Unis, 89183
- OptumCare Cancer Care at Fort Apache
-
Pahrump, Nevada, États-Unis, 89048
- Hope Cancer Care of Nevada-Pahrump
-
Reno, Nevada, États-Unis, 89502
- Renown Regional Medical Center
-
Reno, Nevada, États-Unis, 89503
- Saint Mary's Regional Medical Center
-
Reno, Nevada, États-Unis, 89509
- Radiation Oncology Associates
-
-
New Jersey
-
Hackensack, New Jersey, États-Unis, 07601
- Hackensack University Medical Center
-
Lakewood, New Jersey, États-Unis, 08701
- Monmouth Medical Center Southern Campus
-
Long Branch, New Jersey, États-Unis, 07740
- Monmouth Medical Center
-
Morristown, New Jersey, États-Unis, 07960
- Morristown Medical Center
-
New Brunswick, New Jersey, États-Unis, 08903
- Rutgers Cancer Institute of New Jersey
-
New Brunswick, New Jersey, États-Unis, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
-
New Mexico
-
Albuquerque, New Mexico, États-Unis, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, États-Unis, 12208
- Albany Medical Center
-
Buffalo, New York, États-Unis, 14263
- Roswell Park Cancer Institute
-
New York, New York, États-Unis, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, États-Unis, 10029
- Mount Sinai Hospital
-
New York, New York, États-Unis, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, États-Unis, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, États-Unis, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Stony Brook, New York, États-Unis, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, États-Unis, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, États-Unis, 10467
- Montefiore Medical Center - Moses Campus
-
-
North Carolina
-
Chapel Hill, North Carolina, États-Unis, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, États-Unis, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Clinton, North Carolina, États-Unis, 28328
- Southeastern Medical Oncology Center-Clinton
-
Goldsboro, North Carolina, États-Unis, 27534
- Southeastern Medical Oncology Center-Goldsboro
-
Goldsboro, North Carolina, États-Unis, 27534
- Wayne Memorial Hospital
-
Jacksonville, North Carolina, États-Unis, 28546
- Southeastern Medical Oncology Center-Jacksonville
-
Jacksonville, North Carolina, États-Unis, 28546
- Onslow Memorial Hospital
-
-
North Dakota
-
Fargo, North Dakota, États-Unis, 58103
- Essentia Health Cancer Center-South University Clinic
-
Jamestown, North Dakota, États-Unis, 58401
- Essentia Health - Jamestown Clinic
-
-
Ohio
-
Akron, Ohio, États-Unis, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, États-Unis, 45229
- Cincinnati Children's Hospital Medical Center
-
Cincinnati, Ohio, États-Unis, 45220
- Good Samaritan Hospital - Cincinnati
-
Cincinnati, Ohio, États-Unis, 45242
- Bethesda North Hospital
-
Cincinnati, Ohio, États-Unis, 45247
- TriHealth Cancer Institute-Westside
-
Cincinnati, Ohio, États-Unis, 45255
- TriHealth Cancer Institute-Anderson
-
Cleveland, Ohio, États-Unis, 44109
- MetroHealth Medical Center
-
Columbus, Ohio, États-Unis, 43205
- Nationwide Children's Hospital
-
-
Oklahoma
-
Lawton, Oklahoma, États-Unis, 73505
- Cancer Centers of Southwest Oklahoma Research
-
Oklahoma City, Oklahoma, États-Unis, 73104
- University of Oklahoma Health Sciences Center
-
Oklahoma City, Oklahoma, États-Unis, 73120
- Mercy Hospital Oklahoma City
-
Tulsa, Oklahoma, États-Unis, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
-
-
Oregon
-
Baker City, Oregon, États-Unis, 97814
- Saint Alphonsus Cancer Care Center-Baker City
-
Bend, Oregon, États-Unis, 97701
- Saint Charles Health System
-
Clackamas, Oregon, États-Unis, 97015
- Clackamas Radiation Oncology Center
-
Clackamas, Oregon, États-Unis, 97015
- Providence Cancer Institute Clackamas Clinic
-
Coos Bay, Oregon, États-Unis, 97420
- Bay Area Hospital
-
Newberg, Oregon, États-Unis, 97132
- Providence Newberg Medical Center
-
Ontario, Oregon, États-Unis, 97914
- Saint Alphonsus Cancer Care Center-Ontario
-
Oregon City, Oregon, États-Unis, 97045
- Providence Willamette Falls Medical Center
-
Portland, Oregon, États-Unis, 97213
- Providence Portland Medical Center
-
Portland, Oregon, États-Unis, 97225
- Providence Saint Vincent Medical Center
-
Redmond, Oregon, États-Unis, 97756
- Saint Charles Health System-Redmond
-
-
Pennsylvania
-
Hershey, Pennsylvania, États-Unis, 17033-0850
- Penn State Milton S Hershey Medical Center
-
Philadelphia, Pennsylvania, États-Unis, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, États-Unis, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, États-Unis, 19104
- University of Pennsylvania/Abramson Cancer Center
-
-
South Carolina
-
Boiling Springs, South Carolina, États-Unis, 29316
- Prisma Health Cancer Institute - Spartanburg
-
Columbia, South Carolina, États-Unis, 29203
- Prisma Health Richland Hospital
-
Easley, South Carolina, États-Unis, 29640
- Prisma Health Cancer Institute - Easley
-
Greenville, South Carolina, États-Unis, 29605
- Prisma Health Cancer Institute - Faris
-
Greenville, South Carolina, États-Unis, 29607
- Saint Francis Cancer Center
-
Greenville, South Carolina, États-Unis, 29615
- Prisma Health Cancer Institute - Eastside
-
Greenville, South Carolina, États-Unis, 29605
- Prisma Health Cancer Institute - Butternut
-
Greenville, South Carolina, États-Unis, 29601
- Saint Francis Hospital
-
Greenville, South Carolina, États-Unis, 29605
- BI-LO Charities Children's Cancer Center
-
Greenville, South Carolina, États-Unis, 29605
- Prisma Health Greenville Memorial Hospital
-
Greer, South Carolina, États-Unis, 29650
- Prisma Health Cancer Institute - Greer
-
Seneca, South Carolina, États-Unis, 29672
- Prisma Health Cancer Institute - Seneca
-
-
Tennessee
-
Chattanooga, Tennessee, États-Unis, 37404
- Memorial Hospital
-
Hixson, Tennessee, États-Unis, 37343
- Pulmonary Medicine Center of Chattanooga-Hixson
-
Knoxville, Tennessee, États-Unis, 37916
- East Tennessee Childrens Hospital
-
Memphis, Tennessee, États-Unis, 38105
- Saint Jude Children's Research Hospital
-
Nashville, Tennessee, États-Unis, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, États-Unis, 37203
- The Children's Hospital at TriStar Centennial
-
Ooltewah, Tennessee, États-Unis, 37363
- Memorial GYN Plus
-
-
Texas
-
Austin, Texas, États-Unis, 78723
- Dell Children's Medical Center of Central Texas
-
Bryan, Texas, États-Unis, 77802
- Saint Joseph Regional Cancer Center
-
Corpus Christi, Texas, États-Unis, 78411
- Driscoll Children's Hospital
-
El Paso, Texas, États-Unis, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, États-Unis, 76104
- Cook Children's Medical Center
-
San Antonio, Texas, États-Unis, 78207
- Children's Hospital of San Antonio
-
-
Utah
-
American Fork, Utah, États-Unis, 84003
- American Fork Hospital / Huntsman Intermountain Cancer Center
-
Cedar City, Utah, États-Unis, 84720
- Sandra L Maxwell Cancer Center
-
Logan, Utah, États-Unis, 84321
- Logan Regional Hospital
-
Murray, Utah, États-Unis, 84107
- Intermountain Medical Center
-
Ogden, Utah, États-Unis, 84403
- McKay-Dee Hospital Center
-
Riverton, Utah, États-Unis, 84065
- Riverton Hospital
-
Salt Lake City, Utah, États-Unis, 84106
- Utah Cancer Specialists-Salt Lake City
-
Salt Lake City, Utah, États-Unis, 84143
- LDS Hospital
-
St. George, Utah, États-Unis, 84770
- Saint George Regional Medical Center
-
-
Virginia
-
Norfolk, Virginia, États-Unis, 23507
- Children's Hospital of The King's Daughters
-
-
Washington
-
Aberdeen, Washington, États-Unis, 98520
- Providence Regional Cancer System-Aberdeen
-
Auburn, Washington, États-Unis, 98001
- MultiCare Auburn Medical Center
-
Bellevue, Washington, États-Unis, 98004
- Overlake Medical Center
-
Bellingham, Washington, États-Unis, 98225
- PeaceHealth Saint Joseph Medical Center
-
Burien, Washington, États-Unis, 98166
- Saint Anne Hospital
-
Centralia, Washington, États-Unis, 98531
- Providence Regional Cancer System-Centralia
-
Edmonds, Washington, États-Unis, 98026
- Swedish Cancer Institute-Edmonds
-
Enumclaw, Washington, États-Unis, 98022
- Saint Elizabeth Hospital
-
Everett, Washington, États-Unis, 98201
- Providence Regional Cancer Partnership
-
Federal Way, Washington, États-Unis, 98003
- Saint Francis Hospital
-
Gig Harbor, Washington, États-Unis, 98335
- MultiCare Gig Harbor Medical Park
-
Issaquah, Washington, États-Unis, 98029
- Swedish Cancer Institute-Issaquah
-
Kennewick, Washington, États-Unis, 99336
- Kadlec Clinic Hematology and Oncology
-
Lacey, Washington, États-Unis, 98503
- Providence Regional Cancer System-Lacey
-
Lakewood, Washington, États-Unis, 98499
- Saint Clare Hospital
-
Longview, Washington, États-Unis, 98632
- PeaceHealth Saint John Medical Center
-
Port Townsend, Washington, États-Unis, 98368
- Jefferson Healthcare
-
Poulsbo, Washington, États-Unis, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
-
Puyallup, Washington, États-Unis, 98372
- MultiCare Good Samaritan Hospital
-
Renton, Washington, États-Unis, 98055
- Valley Medical Center
-
Seattle, Washington, États-Unis, 98105
- Seattle Children's Hospital
-
Seattle, Washington, États-Unis, 98107
- Swedish Medical Center-Ballard Campus
-
Seattle, Washington, États-Unis, 98122
- Swedish Medical Center-First Hill
-
Seattle, Washington, États-Unis, 98112
- Kaiser Permanente Washington
-
Seattle, Washington, États-Unis, 98104
- Pacific Gynecology Specialists
-
Seattle, Washington, États-Unis, 98122-5711
- Swedish Medical Center-Cherry Hill
-
Sedro-Woolley, Washington, États-Unis, 98284
- PeaceHealth United General Medical Center
-
Shelton, Washington, États-Unis, 98584
- Providence Regional Cancer System-Shelton
-
Silverdale, Washington, États-Unis, 98383
- Saint Joseph Medical Center Hematology and Oncology - Silverdale
-
Spokane, Washington, États-Unis, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Spokane, Washington, États-Unis, 99204
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
-
Spokane, Washington, États-Unis, 99218
- MultiCare Deaconess Cancer and Blood Specialty Center - North
-
Spokane Valley, Washington, États-Unis, 99216
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
-
Tacoma, Washington, États-Unis, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, États-Unis, 98405
- Northwest Medical Specialties PLLC
-
Tacoma, Washington, États-Unis, 98431
- Madigan Army Medical Center
-
Tacoma, Washington, États-Unis, 98405
- MultiCare Tacoma General Hospital
-
Tacoma, Washington, États-Unis, 98405
- Franciscan Research Center-Northwest Medical Plaza
-
Vancouver, Washington, États-Unis, 98664
- PeaceHealth Southwest Medical Center
-
Walla Walla, Washington, États-Unis, 99362
- Providence Saint Mary Regional Cancer Center
-
Yakima, Washington, États-Unis, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
-
Yelm, Washington, États-Unis, 98597
- Providence Regional Cancer System-Yelm
-
-
West Virginia
-
Bridgeport, West Virginia, États-Unis, 26330
- United Hospital Center
-
Martinsburg, West Virginia, États-Unis, 25401
- WVUH-Berkely Medical Center
-
Morgantown, West Virginia, États-Unis, 26506
- West Virginia University Healthcare
-
Parkersburg, West Virginia, États-Unis, 26101
- Camden Clark Medical Center
-
-
Wisconsin
-
Ashland, Wisconsin, États-Unis, 54806
- Duluth Clinic Ashland
-
Ashland, Wisconsin, États-Unis, 54806
- Northwest Wisconsin Cancer Center
-
Burlington, Wisconsin, États-Unis, 53105
- Aurora Cancer Care-Southern Lakes VLCC
-
Chippewa Falls, Wisconsin, États-Unis, 54729
- Marshfield Clinic-Chippewa Center
-
Eau Claire, Wisconsin, États-Unis, 54701
- Marshfield Medical Center-EC Cancer Center
-
Fond du Lac, Wisconsin, États-Unis, 54937
- Aurora Health Center-Fond du Lac
-
Germantown, Wisconsin, États-Unis, 53022
- Aurora Health Care Germantown Health Center
-
Grafton, Wisconsin, États-Unis, 53024
- Aurora Cancer Care-Grafton
-
Green Bay, Wisconsin, États-Unis, 54311
- Aurora BayCare Medical Center
-
Kenosha, Wisconsin, États-Unis, 53142
- Aurora Cancer Care-Kenosha South
-
La Crosse, Wisconsin, États-Unis, 54601
- Gundersen Lutheran Medical Center
-
Ladysmith, Wisconsin, États-Unis, 54848
- Marshfield Medical Center - Ladysmith
-
Madison, Wisconsin, États-Unis, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marinette, Wisconsin, États-Unis, 54143
- Aurora Bay Area Medical Group-Marinette
-
Marshfield, Wisconsin, États-Unis, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, États-Unis, 53226
- Medical College of Wisconsin
-
Milwaukee, Wisconsin, États-Unis, 53209
- Aurora Cancer Care-Milwaukee
-
Milwaukee, Wisconsin, États-Unis, 53215
- Aurora Saint Luke's Medical Center
-
Milwaukee, Wisconsin, États-Unis, 53233
- Aurora Sinai Medical Center
-
Minocqua, Wisconsin, États-Unis, 54548
- Marshfield Medical Center - Minocqua
-
Oshkosh, Wisconsin, États-Unis, 54904
- Vince Lombardi Cancer Clinic - Oshkosh
-
Racine, Wisconsin, États-Unis, 53406
- Aurora Cancer Care-Racine
-
Rice Lake, Wisconsin, États-Unis, 54868
- Marshfield Medical Center-Rice Lake
-
Sheboygan, Wisconsin, États-Unis, 53081
- Vince Lombardi Cancer Clinic-Sheboygan
-
Stevens Point, Wisconsin, États-Unis, 54482
- Marshfield Medical Center-River Region at Stevens Point
-
Summit, Wisconsin, États-Unis, 53066
- Aurora Medical Center in Summit
-
Two Rivers, Wisconsin, États-Unis, 54241
- Vince Lombardi Cancer Clinic-Two Rivers
-
Wausau, Wisconsin, États-Unis, 54401
- Marshfield Clinic-Wausau Center
-
Wauwatosa, Wisconsin, États-Unis, 53226
- Aurora Cancer Care-Milwaukee West
-
West Allis, Wisconsin, États-Unis, 53227
- Aurora West Allis Medical Center
-
Weston, Wisconsin, États-Unis, 54476
- Marshfield Medical Center - Weston
-
Wisconsin Rapids, Wisconsin, États-Unis, 54494
- Marshfield Clinic - Wisconsin Rapids Center
-
-
Wyoming
-
Cheyenne, Wyoming, États-Unis, 82001
- Cheyenne Regional Medical Center-West
-
Cody, Wyoming, États-Unis, 82414
- Billings Clinic-Cody
-
Sheridan, Wyoming, États-Unis, 82801
- Welch Cancer Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
-
PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
-
Age >= 18 years
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Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
-
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
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Patients may have received other prior activating immunotherapies (i.e. checkpoint inhibitors), but must not have received them within 6 months prior to registration, and there must be no serious unresolved complication of therapy at the time of registration; for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
-
Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
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Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
-
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
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Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10^9/L) (obtained within 2 weeks prior to registration)
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Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
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Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
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Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
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Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
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No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
-
Patient must have no current or prior history of central nervous system (CNS) involvement
-
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
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RANDOMIZED PHASE II (ARMS K AND L): Age >= 12 years
- Pediatric patients will include any patients < 18 years of age
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have relapsed after first line chemotherapy; may have relapsed after autologous stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; patient must not have received a prior allogeneic stem cell transplant (out of risk of reactivation of pulmonary graft versus host disease [GVHD])
-
RANDOMIZED PHASE II (ARMS K AND L): Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients may not have received prior ipilimumab
-
RANDOMIZED PHASE II (ARMS K AND L): Patients may not have received other prior activating immunotherapies (i.e. checkpoint inhibitor therapies); for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
-
RANDOMIZED PHASE II (ARMS K AND L): Adult patient (>= 18 years of age) ECOG-ACRIN performance status between 0-2
- Pediatric patients (16-17 years of age) must have a Karnofsky performance level >= 50%
- Pediatric patients (12-15 years of age) must have a Lansky performance level >= 50
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
-
RANDOMIZED PHASE II (ARMS K AND L): Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
RANDOMIZED PHASE II (ARMS K AND L): Patient of childbearing potential and/or sexually active patient must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both double barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
-
RANDOMIZED PHASE II (ARMS K AND L): Patients with impaired decision-making capacity are eligible with legally authorized representative
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RANDOMIZED PHASE II (ARMS K AND L): Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
-
RANDOMIZED PHASE II (ARMS K AND L): ANC >= 1500/mcL (1.5 x 0^9/L) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): AST/ALT =< 2.5 x upper limit of normal (ULN) for age (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Adult patients (>= 18 years old) must have a calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
-
RANDOMIZED PHASE II (ARMS K AND L): Pediatric patients (< 18 years old) must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine based on age/sex as follows:
-
Age: maximum serum creatinine (mg/dL)
- < 13 years: male (1.2), female (1.2)
- 13 to < 16 years: male (1.5), female (1.4)
- >= 16 years: male (1.7), female (1.4)
-
-
RANDOMIZED PHASE II (ARMS K AND L): No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
-
RANDOMIZED PHASE II (ARMS K AND L): Patient must have no current or prior history of CNS involvement
-
RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
-
RANDOMIZED PHASE II (ARMS K AND L): No history of Steven's Johnson's syndrome, TENs syndrome, or motor neuropathy
-
RANDOMIZED PHASE II (ARMS K AND L): HIV positive patients are eligible provided they meet the other protocol criteria including the following:
- Long term survival expected were it not for the cHL
- HIV viral loads undetectable by standard clinical HIV testing
- Willing to adhere to effective combination antiretroviral therapy
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RANDOMIZED PHASE II (ARMS K AND L): Patients must not have autoimmune disorders, prior solid organ transplant, or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of steroid medication for at least 2 weeks prior to initiation of therapy are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have grade 2 or greater peripheral sensory neuropathy
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
-
RANDOMIZED PHASE II (ARMS K AND L): Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not currently be smoking tobacco or other agents; vaping is not allowed
-
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:
- QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec at baseline
- History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration
- History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
- Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)
- Intra-cardiac defibrillator
- History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
- History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
- Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
Autres noms:
Undergo CT
Autres noms:
Undergo biopsy
Autres noms:
Undergo collection of blood
Autres noms:
Given IV
Autres noms:
Undergo PET
Autres noms:
|
|
Expérimental: 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
Autres noms:
Undergo biopsy
Autres noms:
Undergo collection of blood
Autres noms:
Given IV
Autres noms:
Undergo PET
Autres noms:
Given IV
Autres noms:
|
|
Expérimental: 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
Autres noms:
Undergo CT
Autres noms:
Undergo biopsy
Autres noms:
Undergo collection of blood
Autres noms:
Given IV
Autres noms:
Undergo PET
Autres noms:
Given IV
Autres noms:
|
|
Expérimental: 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
Autres noms:
Undergo biopsy
Autres noms:
Undergo collection of blood
Autres noms:
Given IV
Autres noms:
Undergo PET
Autres noms:
Given IV
Autres noms:
|
|
Expérimental: 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
Autres noms:
Undergo CT
Autres noms:
Undergo biopsy
Autres noms:
Undergo collection of blood
Autres noms:
Given IV
Autres noms:
Undergo PET
Autres noms:
Given IV
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Maximum tolerated dose (MTD) of each combination (Phase I)
Délai: 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)
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Complete response (CR) rate (Phase I)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Effets des associations sur l'immunité systémique (Phase I et II)
Délai: Au départ jusqu'à 6 semaines après la fin du traitement à l'étude
|
Au départ jusqu'à 6 semaines après la fin du traitement à l'étude
|
|
|
Change in the percentage of activated T cells and natural killer cells (Phase I and II)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: Completion of study treatment
|
Will compare the gut microbiome between Hodgkin lymphoma (HL) patients and healthy controls with respect to global diversity, taxonomic abundance, and bacterial functional pathways. The relative abundance of each taxon (phyla to genera) and functional pathways among different groups will be statistically compared in univariate analysis using t-test (or Wilcoxon test) and in multivariate analysis using logistic regression. Global diversity tests and multivariate analysis for taxonomic abundance and functional pathways will be adjusted for potential confounders (age, sex, race, and body mass index) in the comparisons of HL patients and controls, and further adjusted for stage and grade when examining the clinical response among HL patients. |
Completion of study treatment
|
|
Absolute maximum standard uptake value (SUVmax) (Phase II)
Délai: Up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, event free survival (EFS), OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (Kaplan-Meier [KM] curve and log-rank testing). |
Up to cycle 10
|
|
Metabolic whole body tumor volume (MTV) and tumor lesion glycolysis (TLG)
Délai: Up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Up to cycle 10
|
|
Percent change in SUVmax, MTV and TLG between baseline and during therapy
Délai: Baseline up to cycle 10
|
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing). |
Baseline up to cycle 10
|
|
Percent change in size (sum of perpendicular diameters [SPD]) on computed tomography (CT)
Délai: 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
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Catherine S Diefenbach, ECOG-ACRIN Cancer Research Group
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimé)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Peptides
- Acides aminés, peptides et protéines
- Oligopeptides
- Protéines
- Techniques d'investigation
- Techniques de laboratoire clinique
- Techniques et procédures de diagnostic
- Diagnostic
- Procédures chirurgicales, opératoires
- Techniques cytologiques
- Cytodiagnostic
- Facteurs biologiques
- Anticorps, monoclonal, humanisé
- Anticorps, monoclonal
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Techniques de diagnostic, chirurgicale
- Techniques de chimie, analytique
- Analyse du spectre
- Récepteurs, surface cellulaire
- Protéines membranaires
- Antigènes
- Antigènes, surface
- Biomarqueurs
- Récepteurs, immunologique
- Antigènes, différenciation, lymphocyte T
- Antigènes, différenciation
- Protéines de point de contrôle immunitaire
- Récepteurs costimulants et inhibiteurs des cellules T
- Nivolumab
- Ipilimumab
- Brentuximab Védotine
- Biopsie
- Manipulation des échantillons
- Spectroscopie de résonance magnétique
- Antigène CTLA-4
Autres numéros d'identification d'étude
- NCI-2013-01275
- U10CA180820 (Subvention/contrat des NIH des États-Unis)
- U24CA196172 (Subvention/contrat des NIH des États-Unis)
- NCI-2013-01275 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- E4412 (Autre identifiant: CTEP)
- S14-00011
- E4412
- E4412 (Autre identifiant: ECOG-ACRIN Cancer Research Group)
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