Alisertib, Bortezomib, and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or B-cell Low Grade Non-Hodgkin Lymphoma

NCT01695941 | Active Not Recruiting Phase 1

• 6 other identifiers: NCI-2012-01712S12-02028CDR0000740877P90869086P30CA013330
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  21 days

Secondary Outcomes (4)

• Overall response rate (ORR) (complete response and partial response)

  Up to 30 days post-treatment

• Progression free survival (PFS)

  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)

  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

  From time of randomization to the date of death due to any cause, assessed up to 30 days post-treatment

Other Outcomes (1)

• Aurora A expression measured from patient biopsy specimens

  Up to day 8 (course 1)

Study Arms (1)

Treatment (alisertib, bortezomib, and rituximab)

EXPERIMENTAL

Patients receive alisertib PO BID on days 1-7; bortezomib SC on days 1, 8, and 15; and rituximab 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.

Drug: Alisertib; Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Biological: Rituximab

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, LDP-341, LDP341, MLN 341, MLN-341, MLN341, PS 341, PS-341, PS341, Velcade

Treatment (alisertib, bortezomib, and rituximab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib, bortezomib, and rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Treatment (alisertib, bortezomib, and rituximab)

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN 8237, MLN-8237, MLN8237

Treatment (alisertib, bortezomib, and rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed relapsed or refractory mantle cell lymphoma or low grade B-cell non-Hodgkin lymphoma (NHL); patients with evidence of transformation to a high grade histology will not be eligible
• Measurable or evaluable disease, as defined in 2008 Revised Response Criteria for Malignant Lymphoma; baseline scans used for measurement should be obtained within 30 days of registration, and baseline bone marrow biopsy and/or aspiration should be obtained with 90 days of registration
• Patients may have received one or more lines of prior chemotherapy with/without rituximab (including high dose therapy plus stem cell transplant which is counted as one regimen); prior bortezomib is allowed; patients must not have received bortezomib in the past 6 months
• Patients with human immunodeficiency virus (HIV) who are not receiving cytochrome p450 inhibitors, and who have a minimum of 300+ CD4+ cells/mm\^3, an undetectable viral load, and no history of acquired immune deficiency syndrome (AIDS) indicator conditions
• Patients must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL (obtained within 30 days of registration)
• Absolute neutrophil count \>= 1,500/mcL (obtained within 30 days of registration)
• Platelets \>= 75,000/mcL or \>= 50,000/mcL with documented bone marrow involvement (obtained within 30 days of registration)
• Total bilirubin within normal institutional limits (may be elevated if direct bilirubin normal) (obtained within 30 days of registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 3 X institutional upper limit of normal (obtained within 30 days of registration)
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal (obtained within 30 days of registration)
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN8237 administration
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 3 weeks for rituximab) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, bortezomib or rituximab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen, or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
• Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN8237
• HIV-positive patients on combination antiretroviral therapy which include cytochrome p450 inhibitors are ineligible; patients with CD4 counts less than 300 CD4+ cells/mm\^3 and or a high viral load are ineligible
• Grade 2 or greater neuropathy
• The following agents are not permitted while patients are taking MLN8237, and should be discontinued at prior to registration if patients are taking them:
• Patients must stop using the proton pump inhibitor (PPI) for at least 4 days prior to the first dose of MLN8237; administration of PPI while on study is not permitted
• Histamine-2 (H2) receptor antagonists are not permitted from the day prior through to the end of MLN8237 dosing, except as required for premedication for rituximab; constant dosing of H2 blockers is not permitted
• Antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237
• Administration of pancreatic enzymes is not permitted at any time while on study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Mantle-Cell

Interventions

MLN 8237; Bortezomib; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Catherine S Diefenbach

  Montefiore Medical Center - Moses Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: August 31, 2012
• Primary Completion: May 29, 2018
• Study Completion (Estimated): March 3, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (4)