Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation

July 24, 2023 updated by: City of Hope Medical Center

A Phase II Study of Weekly Maintenance Bortezomib and Rituximab in Mantle Cell Lymphoma Post Autologous Hematopoietic Cell Transplantation

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib and rituximab together works in treating patients with mantle cell lymphoma who have previously undergone stem cell transplantation

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the two year disease free survival in mantle cell lymphoma (MCL) patients treated with bortezomib + rituximab after hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile, safety, overall survival, time to treatment failure, remission duration, and biological markers of mantle cell lymphoma patients treated with bortezomib + rituximab after autologous hematopoietic stem cell transplantation.

OUTLINE: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds and rituximab IV on days 1, 8, 15, and 22. Treatment with bortezomib repeats every 3 months for up to 8 courses and treatment with rituximab repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining
  • Patients must have undergone autologous hematopoietic stem cell transplantation (AHCT) and achieved engraftment by day (D)60-180 as evidenced by absolute neutrophil count (ANC) > 1000/mcL and platelets (Plt) > 75,000/mcL
  • Patients must be in complete remission at D60-180 after AHCT as evidenced by computed tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • Male subject agrees to use an acceptable method for contraception for the duration of the study
  • Life expectancy of greater than 3 months
  • Karnofsky > 60%
  • ANC > 1000/mcL
  • Plts > 75,000/mcL
  • Total bilirubin within normal institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal
  • Creatinine up to and including 2 mg/dL

Exclusion Criteria:

  • Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment and at D60-180 after AHCT; patients who had >= grade 2 peripheral neuropathy within 14 days before enrollment but resolves to grade 1 or lower peripheral neuropathy at D60-D180 after AHCT can be enrolled at this time
  • Patient has > 1.5 x upper limit of normal (ULN) total bilirubin unless history of Gilbert's syndrome
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiographic (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  • Patient has hypersensitivity to bortezomib, boron or mannitol
  • Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patient has received other investigational drugs with 14 days before treatment of treatment with bortezomib + rituximab
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
  • Patients with other active malignancies (no evidence of other cancer or life expectancy greater than 5 years) are ineligible for this study
  • Human immunodeficiency virus (HIV) positive patients or hepatitis B or C positive patients
  • Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
  • Prior exposure to either bortezomib or rituximab is not an exclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (bortezomib and rituximab)
Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles.
Other: laboratory biomarker analysis
Correlative studies
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Genetic: DNA analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Names:
  • Pharmacogenomic Study
Genetic: gene expression analysis
Correlative studies
Genetic: RNA analysis
Correlative studies
Drug: bortezomib
Given SC or IV
Other Names:
  • MLN341
  • LDP 341
  • VELCADE
Other: Questionnaire Administration
Other Names:
  • Ancillary Studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two-year Disease-free Survival
Time Frame: Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented.
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two-year Overall Survival
Time Frame: Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year overall survival estimate presented.
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year overall survival estimate presented.
Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment
Time Frame: Participants were followed up to 5 years after initial treatment.
Observed toxicities will be summarized in terms of type, severity (graded by NCI CTCAE version 4.0) and attribution.
Participants were followed up to 5 years after initial treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Matthew Mei, City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 3, 2011

Primary Completion (Actual)

November 2, 2020

Study Completion (Actual)

November 2, 2020

Study Registration Dates

First Submitted

December 27, 2010

First Submitted That Met QC Criteria

December 27, 2010

First Posted (Estimated)

December 29, 2010

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10137 (DAIDS ES)
  • NCI-2010-02343 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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