Brentuximab Vedotin with or without Nivolumab in Treating Patients with Relapsed or Refractory CD30+ Lymphoma
- 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)
- Resolution of all non-hematologic brentuximab vedotin-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
- 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 8 months following the last dose of nivolumab, whichever is later)
I. To estimate the response rate following weekly brentuximab vedotin (1.2 mg/kg 3 of 4 weeks for up to four 28-day cycles) in patients with lack of response (< partial response [PR]) or progression following brentuximab vedotin and demonstrating persistent expression of CD30. (Arm A)
II. To evaluate the response rate of combination brentuximab vedotin and nivolumab in patients with lack of response (< PR) or progression within 6 months following brentuximab vedotin. (Arm B)
I. To monitor clinical outcome following the study treatment regimen.
II. To estimate the frequency of CD30 loss in patients following resistance to brentuximab vedotin.
III. To describe the pattern of CD30 expression (membranous, cytoplasmic, Golgi) in comparison to the pre-brentuximab vedotin expression.
IV. To semi-quantitatively estimate and compare the surface density of CD30 pre and post brentuximab vedotin as measured by flow cytometry.
V. To correlate response with CD30 density as measured by flow cytometry.
VI. To evaluate the tolerability of the weekly regimen in patients previously exposed to brentuximab vedotin.
VII. To explore the tolerability of brentuximab vedotin and nivolumab in patients previously exposed to brentuximab vedotin in a 21-day cycle.
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.
Trial Phase Phase II
Trial Type Treatment
Fred Hutch / University of Washington Cancer Consortium
Ajay Kumar Gopal
- Primary ID 7808
- Secondary IDs NCI-2012-01696
- Clinicaltrials.gov ID NCT01703949