Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma (VCR)

December 16, 2019 updated by: University of Arizona

A Phase II, Open-Label Study of Bortezomib (Velcade), Cladribine and Rituximab (VCR) in Advanced, Newly Diagnosed and Relapsed/Refractory Mantle Cell and Indolent Lymphomas

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 cladribine and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with cladribine and rituximab works in treating patients with advanced mantle cell lymphoma or indolent lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the 2-year progression-free survival of patients with advanced mantle cell lymphoma or indolent lymphoma treated with bortezomib, cladribine, and rituximab.

Secondary

  • Determine the 2-year overall survival of patients treated with this regimen.
  • Determine the complete response and overall response rate in patients treated with this regimen.
  • Describe the long- and short-term toxicity of this regimen in these patients.
  • Determine the prognostic importance of Aurora kinase A in patients treated with this regimen.
  • Determine the cytokine profiles for each lymphoma subtype and how they change with this regimen.
  • Evaluate the prognostic importance of major carcinogenic pathways using tissue microarray.

OUTLINE: Patients receive bortezomib IV on days 1 and 4, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and after course 1 for cytokine profile studies. Previously collected tissue samples are obtained for analysis of Aurora kinase A and B, Ki-67, cyclin D, Bcl-2, phosphor-HisH3, c-Met, and VEGF expression by using tissue microarray (IHC staining), reverse transcriptase-PCR, and/or western blotting.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Study Type

Interventional

Enrollment (Actual)

24

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
    • Arizona
      • Tucson, Arizona, United States, 85724-5024
        • The University of Arizona Cancer Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Voluntary consent before performance of any study-related procedure
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Biopsy-proven mantle cell, marginal zone, lymphoplasmacytic, small lymphocytic lymphoma, or follicular lymphoma
  • CD20-positive disease

  • Patients with marginal zone, lymphoplasmacytic, small lymphocytic, or follicular lymphoma - at least one criterion for initiation of treatment must be met:

    • Symptomatic disease
    • Cytopenia related to lymphoma
    • Leukemic phase (> 5,000 malignant lymphocytes/µl)
    • Mass over 5 cm in greatest diameter
    • For lymphoplasmacytic lymphoma: additional treatment criteria are serum viscosity ≥ 4 cp, serum monoclonal protein > 5 g/L, concurrent primary systemic AL amyloidosis, cold agglutinin disease
  • Age over 18
  • Prior treatment with bortezomib and/or rituximab is acceptable
  • For follicular lymphoma only, at least one prior treatment

Exclusion Criteria:

  • Platelet count of < 100 X10 /L within 14 days before enrollment, unless due to bone marrow infiltration with lymphoma, or due to autoimmune thrombocytopenia because of lymphoma.
  • Patient has an absolute neutrophil count of < 1.0 X 10/L within 14 days before registration, unless due to bone marrow infiltration with lymphoma.
  • Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before registration. (Creatinine Clearance is indicated through the Serum Creatinine. If the Serum Creatinine is abnormal, the physician may then due a 24 hour urine to further clarify Creatinine Clearance. A 24 hour urine test is not required per study.)
  • Patient has ≥ Grade 2 peripheral neuropathy within 14 days before registration.
  • Myocardial infarction within 6 months prior to registration 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.
  • Hypersensitivity to bortezomib, boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant
  • Patient received other investigational drugs with 14 days before registration
  • Serious medical or psychiatric illness likely to interfere with study participation
  • Diagnosed or treated for another malignancy within 3 years of registration, w/ 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.
  • CNS involvement with lymphoma.
  • Known HIV-positive.
  • History of disease refractory to a purine analog (defined as remission duration of < 6 months to therapy that included fludarabine, pentostatin, or cladribine).
  • History of intolerance of bortezomib, boron, mannitol, cladribine, or rituximab.
  • Patient has > 1.5 X ULN Total Bilirubin
  • Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

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: VCR (Velcade, Cladribine and Rituximab)
  • Rituximab 375 mg/m2 IV day1
  • Cladribine 4 mg/m2 IV over 2 hours days 1-5
  • Bortezomib 1.3 mg/m2 IV days 1 and 4
  • Repeat every 28 days for a maximum of 6 cycles
Drug: rituximab
375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles.
Other Names:
  • Rituxan
Drug: bortezomib
1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles.
Other Names:
  • Velcade
Drug: cladribine
4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles.
Other Names:
  • Leustatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival at 2 Years
Time Frame: 2 years
PFS was calculated from the first dose of study drug to the first documentation of disease progression, death regardless of cause, or change in therapy due to disease progression, whichever occurred first. If disease progression did not occur by the end of treatment, patients were evaluated every 3 months until progression with physical examination, laboratory studies, and conventional computed tomographic imaging, up to a maximum of 2 years. The Kaplan-Meier product-limit method will be used to estimate progression-free survival in the presence of censoring.
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival at 2 Years
Time Frame: 2 years
2 years
Complete Response Rate
Time Frame: Two years
Two years
Partial Response
Time Frame: Two years
Two years

Collaborators and Investigators

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

Sponsor

University of Arizona

Collaborators

National Cancer Institute (NCI)

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)

July 7, 2009

Primary Completion (Actual)

September 12, 2014

Study Completion (Actual)

August 14, 2018

Study Registration Dates

First Submitted

September 18, 2009

First Submitted That Met QC Criteria

September 18, 2009

First Posted (Estimate)

September 21, 2009

Study Record Updates

Last Update Posted (Actual)

December 30, 2019

Last Update Submitted That Met QC Criteria

December 16, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0800001071 (Other Identifier: UofA IRB #)
  • P30CA023074 (U.S. NIH Grant/Contract)
  • UARIZ-08-1071-04 (Other Identifier: UofA IRB)
  • X05260 (Other Identifier: Sponsor Protocol ID)
  • CDR0000655078 (Other Identifier: OLD PDQ #)
  • 08-1071-04 (Other Identifier: UofA IRB #)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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