This phase II trial studies how well ixazomib and rituximab work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond (refractory) to BTK inhibitor treatment. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with rituximab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib and rituximab may work better in treating patients with mantle cell lymphoma compared to rituximab alone.
PRIMARY OBJECTIVES: I. To evaluate the complete remission rate of Bruton's tyrosine kinase (BTK) inhibitor refractory mantle cell lymphoma (MCL) patients with ixazomib citrate (ixazomib) and rituximab at 16 weeks of therapy. SECONDARY OBJECTIVES: I. To evaluate overall response rate (ORR) assessed by Lugano criteria. II. To evaluate progression free survival (PFS) and overall survival (OS). III. To evaluate the safety and tolerability. TERTIARY/EXPLORATORY OBJECTIVES: I. To evaluate biomarkers of response to treatment and mechanisms of resistance with pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry. OUTLINE: Patients receive ixazomib orally (PO) on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab IV over 4-8 hours on day 1. Treatment repeats every 28 days up to cycle 12 in the absence of disease progression or unacceptable toxicity. Patients benefiting from treatment may continue to receive ixazomib indefinitely in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
M D Anderson Cancer Center
Houston, Texas, United States
Complete Remission Rate at 16 Weeks
Evaluate the complete remission rate of BTK inhibitor refractory MCL patients with ixazomib and rituximab at 16 weeks of therapy. Complete remission at 16 weeks was measured by PET/CT or CT imaging using Lugano Criteria 2014.
Time frame: 16 weeks
Overall Response Rate at 16 Weeks
Evaluate the overall response rate (ORR) assessed by Lugano criteria (2014)
Time frame: 16 weeks
Progression Free Survival (PFS) and Overall Survival (OS)
Evaluate progression free survival and overall survival
Time frame: 16 weeks
Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56
Tolerability of study drug at weeks 8, 16, 28, 42, and 56 using CTCAE v4.0 Toxicities or Adverse Events (grade 3 and up) were measured using CTCAE v 4.0 to determine the tolerability of ixazomib.
Time frame: time of first dose of ixazomib through 30 days after the last dose of ixazomib was administered, up to 140 weeks.
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