This phase I trial studies the side effects and best dose of duvelisib when given together with nivolumab in treating patients with Richter syndrome or transformed follicular lymphoma. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 duvelisib and nivolumab may work better in treating patients with Richter syndrome or transformed follicular lymphoma compared to giving duvelisib or nivolumab alone.
PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD) of duvelisib in combination with nivolumab for patients with Richter?s syndrome or transformed follicular lymphoma. SECONDARY OBJECTIVES: I. To assess preliminary efficacy of duvelisib in combination with nivolumab in Richter?s syndrome and transformed follicular lymphoma (overall response rate, progression free survival, overall survival). II. To determine the toxicity profile of duvelisib in combination with nivolumab. EXPLORATORY OBJECTIVES: I. To correlate response to duvelisib in combination with nivolumab with cytogenetic/fluorescence in-situ hybridization (FISH) abnormalities of the chronic lymphocytic leukemia (CLL) and lymphoma compartments (for patients with Richter?s syndrome) at baseline. II. To correlate response to duvelisib in combination with nivolumab with baseline deoxyribonucleic acid (DNA) mutation of CLL and lymphoma as assessed in tumor samples and cell free DNA. III. To determine changes in T, B, and natural killer (NK) cell number and function during duvelisib plus nivolumab therapy. OUTLINE: This is a dose-escalation study of duvelisib. Patients receive duvelisib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Maximum-tolerated dose (MTD) of duvelisib
The MTD is defined as the highest dose level where at most one patient out of six experiences dose-limiting toxicities.
Time frame: Up to 28 days
Overall response rate
Will be defined as the proportion of patients achieving a complete or partial response; any eligible patient who begins treatment with the combination regimen will be included in the denominator. Will be calculated with a 95% binomial confidence interval.
Time frame: Up to 3 years
Progression-free survival (PFS)
The method of Kaplan Meier will be used to estimate PFS.
Time frame: From cycle 1, day 1 to date of progression or death, assessed up to 3 years
Overall survival (OS)
The method of Kaplan Meier will be used to estimate OS.
Time frame: From cycle 1, day 1 to date of progression or death, assessed up to 3 years
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