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

This study has been completed.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
University of Rochester
Genentech, Inc.
Biogen Idec
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00117156
First received: June 30, 2005
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
MALT Lymphoma
Drug: Fludarabine
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: Assessed after three- and six-cycles of therapy. ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.


Enrollment: 26
Study Start Date: December 2003
Study Completion Date: January 2012
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Fludarabine Drug: Rituximab

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%.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117156

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
United States, New York
University of Rochester Cancer Center
Rochester, New York, United States, 14627
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
University of Rochester
Genentech, Inc.
Biogen Idec
Investigators
Principal Investigator: Jennifer R. Brown, MD, PhD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Jennifer R. Brown, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00117156     History of Changes
Other Study ID Numbers: 03-294
Study First Received: June 30, 2005
Results First Received: September 26, 2014
Last Updated: October 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
Fludarabine
Rituximab
Marginal Zone Lymphoma
MALT lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Rituximab
Fludarabine
Fludarabine phosphate
Vidarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014