This phase II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may find cancer cells and help kill them. Giving ibrutinib and rituximab may be an effective treatment for mantle cell lymphoma.
PRIMARY OBJECTIVES: I. To evaluate the response rate of ibrutinib plus rituximab in patients with relapsed and/or refractory mantle cell lymphoma (MCL). II. To evaluate the safety and response rate of ibrutinib plus rituximab in elderly patients (\> 65) with newly-diagnosed, untreated MCL. SECONDARY OBJECTIVES: I. To further evaluate the toxicity profile of the combination of ibrutinib and rituximab in patients with relapsed and/or refractory MCL. II. To estimate the overall response rate (ORR); (partial response \[PR\] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS) in patients with relapsed and/or refractory MCL; clinical benefit response (CBR) = (minimal response \[MR\] + ORR) will also be evaluated. III. To estimate the response duration, PFS, time to progression (TTP), and OS in elderly patients (\> 65) with newly-diagnosed, untreated MCL. EXPLORATORY OBJECTIVES: I. To correlate detected gene mutations and changes in gene and/or protein expression with response to treatment. OUTLINE: Patients receive ibrutinib orally (PO) daily on days 1-28 and rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib 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 1 year and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
113
M D Anderson Cancer Center
Houston, Texas, United States
Overall response (complete response and partial response), assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma
Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.
Time frame: Up to 8 weeks
Overall response (complete response and partial response) in elderly patients with newly-diagnosed, untreated mantle cell lymphoma, assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma
Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.
Time frame: Up to 8 weeks
Incidence of toxicity, defined as grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2
Toxicity data will be summarized by frequency tables for all patients.
Time frame: Up to 4 weeks
Incidence of grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2 in newly diagnosed elderly patients
Toxicity data will be summarized by frequency tables for all patients.
Time frame: Up to 4 weeks
Clinical benefit response (minimal response + overall response rate),
Will be assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma.
Time frame: Up to 6 years
Duration of response
Duration of response will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.
Time frame: Up to 6 years
Progression-free survival
Progression-free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.
Time frame: Up to 6 years
Time to progression
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.
Time frame: Up to 6 years
Overall survival
Overall survival will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.
Time frame: Up to 6 years
Duration of response in elderly patients with newly diagnosed, untreated mantle cell lymphoma
Intend-to-treat analysis will be applied to the eligible patients.
Time frame: Up to 6 years
Progression-free survival in elderly patients with newly diagnosed, untreated mantle cell lymphoma
Intend-to-treat analysis will be applied to the eligible patients.
Time frame: Up to 6 years
Overall survival in elderly patients with newly diagnosed, untreated mantle cell lymphoma
Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.
Time frame: Up to 6 years
Time to progression in elderly patients with newly diagnosed, untreated mantle cell lymphoma
Time frame: Up to 6 years
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