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

Primary Purpose

Lymphoma, Non-Hodgkin, MALT Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Rituximab
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Fludarabine, Rituximab, Marginal Zone Lymphoma, MALT lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • University of Rochester Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine and Rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective Response Rate
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
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
3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.

Full Information

First Posted
June 30, 2005
Last Updated
July 28, 2016
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, University of Rochester, Genentech, Inc., Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT00117156
Brief Title
Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma
Official Title
A Phase II Study of Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, University of Rochester, Genentech, Inc., Biogen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin, MALT Lymphoma
Keywords
Fludarabine, Rituximab, Marginal Zone Lymphoma, MALT lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fludarabine and Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Rituximab
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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).
Time Frame
Assessed after three- and six-cycles of therapy.
Secondary Outcome Measure Information:
Title
3.1-Year Progression-Free Survival
Description
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).
Time Frame
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
Title
3.1-Year Overall Survival
Description
3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.
Time Frame
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer R. Brown, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Rochester Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14627
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19344412
Citation
Brown JR, Friedberg JW, Feng Y, Scofield S, Phillips K, Dal Cin P, Joyce R, Takvorian RW, Fisher DC, Fisher RI, Liesveld J, Marquis D, Neuberg D, Freedman AS. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol. 2009 Jun;145(6):741-8. doi: 10.1111/j.1365-2141.2009.07677.x. Epub 2009 Mar 30.
Results Reference
result

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

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