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Recurrent B-Cell Non-Hodgkin LymphomaPhase 1NCT01695941

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

A Phase 1 study testing Alisertib, Bortezomib and Laboratory Biomarker Analysis in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alisertib, Bortezomib and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
4 sitesUnited States
Study dates
31 Aug 2012to 3 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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

Who cannot join

  • 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
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  • 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
  • Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine or St. John's wort is not permitted
  • Concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; if bisphosphonate therapy is initiated after study entry, bone lesions will not be considered evaluable for disease response
  • Patients must be willing not drive, operate dangerous tools or machinery, or engage in any other potentially hazardous activity that requires full alertness and coordination if they experience excessive sedation; if a patient experiences excessive sedation believed to be related to MLN8237, treatment with MLN8237 should be interrupted
  • Patients must be willing to limit alcohol consumption to no more than 1 standard unit of alcohol (12 oz beer [350 mL], 1.5 oz [45 mL] of 80-proof alcohol, or one 6-oz [175 mL] glass of wine) per day during the study and for 30 days from the last dose of MLN8237; minimize the use of agents with central nervous system (CNS) effects
  • Benzodiazepine use is discouraged but not prohibited

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: A Phase I Study of MLN8237 in Combination With Bortezomib and Rituximab in Relapsed and Refractory Mantle Cell and Low Grade Non-Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Alisertib, Bortezomib, Laboratory Biomarker Analysis, Rituximab
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlisertibDrug

    Also called Aurora A Kinase Inhibitor MLN8237, MLN 8237, MLN-8237, MLN8237

    Given PO

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, Boruzu, LDP 341, LDP-341

    Given SC

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

Study groups in NCT01695941
Study groupRoleWhat they receive
Treatment (alisertib, bortezomib, and rituximab)ExperimentalPatients 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.
Receives: Drug: Alisertib; Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 21 days

  2. 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.

    Measured: 21 days

Secondary outcomes (4)

  1. Overall response rate (ORR) (complete response and partial response)

    ORR will be summarized descriptively.

    Measured: Up to 30 days post-treatment

  2. Progression free survival (PFS)

    Kaplan-Meier methodology will be used to summarize estimate median PFS for patients in all treatment groups.

    Measured: 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

  3. Duration of response (DOR)

    Kaplan-Meier methodology will be used to summarize estimate median DOR for patients in all treatment groups.

    Measured: 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

  4. Overall survival

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2012 (estimated)
  2. Study start31 Aug 2012
  3. Primary completion29 May 2018
  4. Study completion3 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01695941
Sponsor's protocol ID
NCI-2012-01712
Other IDs
NCI-2012-01712, S12-02028, CDR0000740877, P9086, 9086, 9086, P30CA013330
Status last verified
Sep 2026
First submitted
26 Sep 2012
Last updated
4 Sep 2026
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alisertib, Bortezomib and Laboratory Biomarker Analysis in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01695941.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.

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