This phase II trial studies how well obinutuzumab works in combination with ibrutinib in treating patients with mantle cell lymphoma that has returned (relapsed) or that does not respond to treatment (refractory). Obinutuzumab binds to a protein called cluster of differentiation (CD)20, which is found on B cells and some types of leukemia and lymphoma cells and help the immune system kill cancer cells. Ibrutinib blocks a protein called Bruton's tyrosine kinase (BTK), which may help keep cancer cells from growing. Giving obinutuzumab in combination with ibrutinib may kill more cancer cells.
PRIMARY OBJECTIVE: I. Best overall response of complete response/partial response (CR/PR). SECONDARY OBJECTIVES: I. Toxicity defined as any adverse event (AE) grade 3 and higher. II. Progression free survival. EXPLORATORY/CORRELATIVE OBJECTIVES: I. Gene expression profiling using Lymph5Cx test. II. Sequencing using the ion torrent platform (76 gene panel for known mutations in lymphoma). III. Sequencing of BTK and phospholipase-C gamma (PLC) to evaluate for mutations. IV. Minimal residual disease testing (MRD by flow cytometry and targeted sequencing post treatment). OUTLINE: Patients receive obinutuzumab intravenously (IV) over 30 minutes on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-6. Patients also receive ibrutinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving partial response (PR) continue to receive obinutuzumab IV every 2 months and ibrutinib PO QD for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given PO
Given IV
OHSU Knight Cancer Institute
Portland, Oregon, United States
Percent of Participants With Best Overall Objective Response or Complete Response/Partial Response (CR/PR)
Overall response is measured combining bone marrow biopsy with CT or PET, measuring target and evaluable non-targeted lesions, according to the Lugano criteria. For FDG-PET, the Deauville criteria is used in conjecture with CT to assess lesion FDG-update. Deauville scale ranges from 1 to 5, where 1 is best (no uptake or no residual uptake) and 5 is worst (markedly increased uptake or any new lesion). If bone marrow is involved prior to treatment, infiltrate must have cleared on repeat biopsy for CR; bone marrow assessment is irrelevant for determination of PR. Measurements are taken at baseline, end of cycle 2, end of induction (after cycle 6) and every 4 months thereafter. Best overall response is any CR or PR reported since start of therapy. Percent of participants with complete response or partial response (CR+PR) are reported along with 95% confidence interval.
Time frame: From first dose of study therapy until the 6-month disease assessment (Cycle 6, Day1 or End of Induction Day 28). Disease assessment is also assessed at end of Cycle 2 (2-months).
Progression Free Survival (PFS)
Median progression free survival is measured from first day of study therapy until disease progression or death, whichever comes first. Participants who progress prior to their first scheduled disease assessment are considered to have clinically progressed. Participants who do not progress are censored at the time of their last disease assessment. The Kaplan-Meier method is used to estimate median PFS. 95% confidence interval is provided, although upper limit was not achieved (insufficient number of progressions)
Time frame: Time from the first day of combined study treatment to disease progression or death, whichever occurs first, assessed up to approximately 4 years, 11 months, after first dose of study drug(s)
Number of Participants With Treatment-related Toxicities, Grade 3 or Higher, as Assessed by CTCAE v4.0
Defined as any adverse event grade 3 or higher, classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, from the first dose of study drug(s) until 30 days after the last dose of study drug(s)
Time frame: Measured from the first dose of either study drug until 30 days after the last dose of study drug, for approximately 4 years, 11 months.
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