Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma

July 28, 2016 updated by: Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute

A Phase II Study of Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma

The purpose of this study is to determine the effectiveness of six cycles of concurrent fludarabine and rituximab in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphoma (MZL) or CD5-, CD10-, CD20+ low-grade B cell lymphomas.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objectives:

Primary

- To estimate the objective response rate.

Secondary

  • To assess the safety.
  • To describe the progression-free survival at one year.
  • To examine the association between clonal cytogenetic abnormalities identified by FISH, and the objective response rate as well as the progression-free survival at one year.

Target enrollment was 30 eligible patients. An 80% objective response rate at 1 month restaging after 6 cycles was considered as evidence of activity in this patient population while 60% was not considered activity. If at least 22 patients achieved objective response the treatment would be considered promising. With 30 eligible patients, the probability of observing this was 0.87 assuming a true rate of 80% and 0.09 assuming a true rate of 60%.

Study Type

Interventional

Enrollment (Actual)

26

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
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center
    • New York
      • Rochester, New York, United States, 14627
        • University of Rochester 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:

  • Histologically confirmed, newly diagnosed or relapsed MALT, marginal zone lymphoma, or low-grade B cell lymphoproliferative disorder which is CD5-, CD10- and CD20+
  • Pathology must be reviewed at Brigham & Women's Hospital, Massachusetts General Hospital, or the University of Rochester James P. Wilmot Cancer Center prior to enrollment
  • Documentation of CD20+ status
  • Must not be a candidate for local radiotherapy with curative intent
  • If gastric MALT, not a candidate for antibiotic therapy with curative intent
  • Patients with leukemic phase marginal zone lymphoma are eligible if their absolute lymphocyte count is >10,000 / µl
  • Prior treatment with rituximab is permitted, if rituximab induced an objective response which persisted for at least 6 months
  • Prior radiotherapy is acceptable
  • Measurable disease
  • ANC: > 1000/mm3
  • Platelets: > 100,000/mm3
  • Hemoglobin: > 7 gm/dL
  • Adequate renal function as indicated by serum creatinine <= 2 mg/dL.
  • Adequate liver function, as indicated by serum total bilirubin <= 2 mg/dL.
  • AST or ALT <3x Upper Limit of Normal unless related to primary disease.
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during study treatment and for six months after completion of study treatment.
  • WHO Performance status </= 2
  • Subject has provided written informed consent.

Exclusion Criteria:

  • Patients with Waldenstrom's Macroglobulinemia or lymphoplasmacytic lymphoma are excluded
  • History of HIV
  • Active infection
  • Known CNS disease
  • Pregnant (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or currently lactating women
  • Prior treatment within the last three weeks
  • Prior fludarabine
  • Positive direct antiglobulin test

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: Fludarabine and Rituximab

Fludarabine:

25 mg/m2 on days 1-5 of 28 day cycle up to 6 cycles

Rituximab:

375 mg/m2 on day 1 of 28 day cycle up to 6 cycles Rituximab dose was split between days 1 and 3 for patients with absolute lymphocyte counts > 10x10^9/L

Patients received three cycles of therapy followed by re-staging with chest/ abdomen/ pelvic CT scan. Patients with progressive disease discontinued treatment. Patients with stable or responding disease continued therapy for another 3 cycles.
Drug: Rituximab
Drug: Fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: Assessed after three- and six-cycles of therapy.
Objective response rate is defined as the proportion of patients who achieve complete remission (CR), complete remission/unconfirmed (CRu) or partial remission (PR) based on Cheson criteria (1999).
Assessed after three- and six-cycles of therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3.1-Year Progression-Free Survival
Time Frame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
3.1-year progression-free survival is the probability of patients remaining alive and progression-free at 3.1 years from study entry estimated using Kaplan-Meier methods. Disease progression was assessed per Cheson criteria (1999).
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
3.1-Year Overall Survival
Time Frame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years

Collaborators and Investigators

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

Sponsor

Dana-Farber Cancer Institute

Collaborators

Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Genentech, Inc.
Biogen
University of Rochester

Investigators

  • Principal Investigator: Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute

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

December 1, 2003

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

June 30, 2005

First Submitted That Met QC Criteria

June 30, 2005

First Posted (Estimate)

July 4, 2005

Study Record Updates

Last Update Posted (Estimate)

August 1, 2016

Last Update Submitted That Met QC Criteria

July 28, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-294

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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