This phase I trial studies the side effects and best dose of alisertib and bortezomib when given together with rituximab in treating patients with mantle cell lymphoma or B-cell low grade non-Hodgkin lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Alisertib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving alisertib and bortezomib together with rituximab may be a better treatment for relapsed or refractory mantle cell lymphoma or B-cell low grade non-Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. To determine the recommended phase II dose of alisertib (MLN8237) and bortezomib when combined with rituximab in patients with relapsed/refractory mantle cell and B-cell low grade non-Hodgkin lymphoma. SECONDARY OBJECTIVES: I. To describe the rate of overall response (complete response and partial response) for patients with relapsed/refractory mantle cell and B-cell low grade non-Hodgkin lymphoma treated with the combination of MLN8237 plus bortezomib and rituximab. TRANSLATIONAL OBJECTIVES: I. To evaluate the clinical significance of Aurora A over-expression and the proliferative index in initial tumor biopsy specimens from patients with relapsed/refractory mantle cell and B-cell low grade non-Hodgkin lymphoma treated with the combination of MLN8237 plus bortezomib and rituximab. II. To evaluate and compare in paired biopsy specimens pre-treatment and on day 8: apoptosis and G2M arrest, and the expression level of cell cycle related proteins including: cyclin D1, p53, BIM-1, p27, p21, noxa, puma and survivin. OUTLINE: This is a dose-escalation study of alisertib and bortezomib. Patients receive alisertib orally (PO) twice daily (BID) on days 1-7; bortezomib subcutaneously (SC) on days 1, 8, and 15; and rituximab intravenously (IV) on day 1. Treatment repeats every 28 days\* in the absence of disease progression or unacceptable toxicity. Note: \*After 8 courses, treatment with rituximab repeats once every 3 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Recommended phase II dose of alisertib when combined with bortezomib and rituximab, defined as the highest dose level at which < 33% of the dose cohort experience a dose limiting toxicity (DLT)
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities will be described by intensity at each dose level.
Time frame: 21 days
Recommended phase II dose of bortezomib when combined with alisertib and rituximab, defined as the highest dose level at which < 33% of the dose cohort experience a dose limiting toxicity (DLT)
Graded using the NCI CTCAE version 5.0. Toxicities will be described by intensity at each dose level.
Time frame: 21 days
Overall response rate (ORR) (complete response and partial response)
ORR will be summarized descriptively.
Time frame: Up to 30 days post-treatment
Progression free survival (PFS)
Kaplan-Meier methodology will be used to summarize estimate median PFS for patients in all treatment groups.
Time frame: From time of study entry to the first documentation of tumor progression or death due to any cause, whichever comes first, assessed up to 30 days post-treatment
Duration of response (DOR)
Kaplan-Meier methodology will be used to summarize estimate median DOR for patients in all treatment groups.
Time frame: From time of documentation of a response to treatment to the first documentation of documentation of tumor progression or death due to any cause whichever comes first, assessed up to 30 days post-treatment
Overall survival
Time frame: From time of randomization to the date of death due to any cause, assessed up to 30 days post-treatment
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