Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma

In brief

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.

Key facts

Study ID

NCT01896999

Run by

National Cancer Institute (NCI)

People needed

146

Starts

2014-03-07

Expected to finish

2026-12-31

Last updated by the study team

2026-07-02

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
• Age >= 18 years
• Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
• Patients must have relapsed after first line chemotherapy; may have relapsed after autologous or allogeneic stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; if status post allogeneic stem cell transplant, no active graft versus host disease
• Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients in the nivolumab/brentuximab cohorts ONLY (D, E, F, Y) may have received prior ipilimumab
• Patients may have received other prior activating immunotherapies (i.e. checkpoint inhibitors), but must not have received them within 6 months prior to registration, and there must be no serious unresolved complication of therapy at the time of registration; for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
• Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
• Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
• Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patient of childbearing potential and/or sexually active patients must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both single barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
• Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
• Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
• Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10\^9/L) (obtained within 2 weeks prior to registration)
• Platelets >= 75,000/mcL (75 x 10\^9/L) (obtained within 2 weeks prior to registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
• Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
• Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
• No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
• Patient must have no current or prior history of central nervous system (CNS) involvement
• All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
• No history of Steven's Johnson's syndrome, toxic epidermal necrolysis (TEN)s syndrome, or motor neuropathy
• Human immunodeficiency virus (HIV) positive patients are allowed on this study if they have a CD4 count > 400, and are on a stable antiviral regimen; patients with poorly controlled HIV or other chronic active viral infections will be excluded
• Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed
• Replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to initiation of study treatment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
• Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible

Where it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States
• Kingman Regional Medical Center — Kingman, Arizona, United States
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• Kaiser Permanente-Deer Valley Medical Center — Antioch, California, United States
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande, California, United States
• PCR Oncology — Arroyo Grande, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Kaiser Permanente Dublin — Dublin, California, United States
• Kaiser Permanente-Fremont — Fremont, California, United States
• Fresno Cancer Center — Fresno, California, United States
• Kaiser Permanente-Fresno — Fresno, California, United States
• Kaiser Permanente-Modesto — Modesto, California, United States
• Kaiser Permanente Oakland-Broadway — Oakland, California, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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