Refractory Classic Hodgkin Lymphoma Clinical Trial
Official title:
A Phase 1 Study of CC-486 Plus Nivolumab in Patients With Hodgkin Lymphoma Refractory to PD-1 Therapy
This phase I trial tests the safety and best dose of CC-486 (an oral form of azacitidine) when given together with nivolumab in treating patients with Hodgkin lymphoma that does not respond (refractory) to PD1-based immunotherapy or has come back (relapsed). CC-486 is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CC-486 in combination with nivolumab may render nivolumab more effective.
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining oral azacitidine (CC-486) and nivolumab in patients with Hodgkin lymphoma (HL) refractory to PD1/PD-L1 therapy. II. Estimate the overall response rate (ORR) in patients treated with CC-486 plus nivolumab. SECONDARY OBJECTIVE: I. Estimate the complete response (CR) rate, duration of response (DOR), progression-free survival (PFS) and overall survival (OS) in patients treated with CC-486 plus nivolumab. EXPLORATORY OBJECTIVES: I. Examine the association between clinical outcomes with nivolumab + CC-486 and circulating tumor-derived deoxyribonucleic acid (ctDNA) characteristics (mutation profile, kinetics of clearance). II. Examine changes in peripheral blood immune subsets, clonality, and T-cell receptor (TCR) repertoire during treatment with nivolumab and CC-486. III. Examine the pre-treatment cellular spatial relationships in the tumor microenvironment by geographical mapping and assess association with response. IV. Explore the association between baseline total metabolic tumor volume, complete response, and PFS after CC-486 plus nivolumab therapy. V. Explore the association between change in total metabolic tumor volume between baseline and 16 weeks, complete response, and PFS after CC-486 plus nivolumab therapy. VI. Explore the association between outcomes (overall response, complete response, PFS) and other baseline quantitative positron emission tomography (PET) (qPET) parameters including total lesion glycolysis and standardized uptake value maximum (SUVmax). OUTLINE: This is a dose-expansion study of azacitidine. Patients receive azacitidine orally (PO) once daily (QD) on days 1-7 and nivolumab intravenously (IV) over 30 minutes on day 8. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 12 weeks for 1 years, and then every 24 weeks for 1 year. ;
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