This phase I study studies the side effects and best dose of venetoclax and lenalidomide when given together with obinutuzumab in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or not responding to treatment. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving obinutuzumab, venetoclax, and lenalidomide may work better in treating patients with B-cell non-Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D), which is typically the maximum tolerated dose (MTD), of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). SECONDARY OBJECTIVES: I. To estimate the overall objective response rate to the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell NHL. II. To estimate the duration of response and 2 year progression-free survival associated with obinutuzumab, venetoclax, and lenalidomide treatment in patients with relapsed and refractory B-cell NHL. III. To define the qualitative and quantitative toxicities of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell NHL. OUTLINE: This is a dose-escalation study of venetoclax and lenalidomide. Patients receive lenalidomide orally (PO) on days 1-21 and venetoclax PO on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years, then every 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Emory University
Atlanta, Georgia, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
MTD defined as the highest level at which no more than 6 patients experience a DLT assessed by National Cancer Institute Common Terminology Criteria of Adverse Events version 4
The recommended phase 2 dose (RP2D), which is typically the maximum tolerated dose (MTD), of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).
Time frame: Up to 28 days
Objective response rate (ORR) defined as the proportion of patients achieving a complete or partial, response according to the Lugano Lymphoma Response Criteria
ORR will be reported with a 95% binomial confidence interval.
Time frame: Up to 3 years
Progression-free survival
PFS will be estimated using the method of Kaplan-Meier. Median PFS and 2-year PFS estimates will be reported with 95% confidence intervals. If applicable, a sensitivity analysis of PFS will include any eligible patient who receives at least one dose of study treatment (i.e. venetoclax alone without beginning the combination regimen).
Time frame: From course 1 day 1 to the date of the event (i.e., death or disease progression), assessed up to 2 years
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