Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma

OUTLINE:

ARM A (CLOSED TO ACCRUAL): Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3-5 weeks, every 3 months for 1 year, and then every 6 months for 4 years.

Inclusion criteria

• Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or progressed within 6 months of the last dose of brentuximab vedotin
• Documented expression of CD30 on tumor cells
• Absolute neutrophil count (ANC) > 1,000/uL
• Platelets > 50,000/uL
• Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
• Bilirubin < 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
• Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance imaging [MRI]) criteria (> 1.5 cm). (Patients with cutaneous lymphoma only require measurable disease by Olsen Criteria)
• Age >= 18 yrs at the time of the first dose of study drug
• Resolution of all non-hematologic brentuximab vedotin-related and nivolumab-related adverse events (AEs) to < Grade 2
• All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
• Patients must be anticipated to complete at least 2 cycles of chemotherapy on study
• Expected survival if untreated of > 90 days

Exclusion criteria

• Prior transplant within 100 days
• Radioimmunotherapy within 12 weeks
• Known human immunodeficiency virus (HIV) or hepatitis B positivity or prior progressive multifocal leukoencephalopathy (PML)
• Active infection or other medical condition which would preclude treatment in the opinion of the principal investigator; this would include a corrected diffusing capacity of the lungs for carbon monoxide (DLCO) of < 60% predicted or symptomatic interstitial lung disease
• Eastern Cooperative Oncology Group (ECOG) performance status > 2
• Known active central nervous system (CNS) involvement
• Peripheral neuropathy > grade 1 if due to brentuximab vedotin or any peripheral neuropathy > grade 2
• Intolerance to brentuximab vedotin
• Concurrent use of other anti-cancer agents or experimental treatments
• No current or prior autoimmune disease with the exception of vitiligo and autoimmune alopecia (Arm B only)
• Pregnancy or breastfeeding; (females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin [beta-hCG] pregnancy test result within 7 days prior to the first dose of brentuximab vedotin; females with false positive results and documented verification that the patient is not pregnant are eligible for participation; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 6 months following the last dose of brentuximab vedotin or 6 months following the last dose of nivolumab, whichever is later)