This phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.
PRIMARY OBJECTIVE: I. To compare the 2-year progression-free survival (PFS) rate in treated patients. SECONDARY OBJECTIVE: I. To determine safety and tolerability, the overall response rate (ORR), the estimated PFS, changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels) and biomarker responses in relapsed chronic lymphocytic leukemia (CLL) patients receiving ibrutinib (i) versus ibrutinib and rituximab (iR). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab intravenously (IV) over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 60 days and then every 4 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
M D Anderson Cancer Center
Houston, Texas, United States
Progression-free survival rate
A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
Time frame: Time from start of treatment to progression or death date, assessed at 2 years
Incidence of adverse events
Toxicity will be reported by type, frequency and severity. Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements.
Time frame: Up to 5 years
Overall response rate
Wilcoxon rank test will be used in the data analyses of continuous variables.
Time frame: Up to 5 years
Estimated progression-free survival
Time to progression functions will be estimated using the Kaplan-Meier method. A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
Time frame: Up to 5 years
Changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels)
Will be assessed by flow cytometry.
Time frame: Baseline to up to 5 years
Quality of life (QOL)
Will be assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30). Analyzed by linear mixed models for longitudinal data. These models allow each patient to have a random intercept and a random slope, which describe their differences at baseline and their different changing trends over time.
Time frame: Up to 24 cycles (96 weeks)
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