This phase II pilot trial studies how well brentuximab vedotin with or without nivolumab works in treating patients with CD30+ lymphoma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work better in treating patients with CD30+ lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01703949.
PRIMARY OBJECTIVES:
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)
EXPLORATORY OBJECTIVES:
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.
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.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorAjay Kumar Gopal
