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

Phase 2
Completed
Conditions
Lymphoma, Non-Hodgkin
MALT Lymphoma
Interventions
Registration Number
NCT00117156
Lead Sponsor
Dana-Farber Cancer Institute
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%.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Fludarabine and RituximabRituximabFludarabine: 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.
Fludarabine and RituximabFludarabineFludarabine: 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.
Primary Outcome Measures
NameTimeMethod
Objective Response RateAssessed 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).

Secondary Outcome Measures
NameTimeMethod
3.1-Year Progression-Free SurvivalAssessed 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).

3.1-Year Overall SurvivalAssessed 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.

Trial Locations

Locations (4)

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University of Rochester Cancer Center

🇺🇸

Rochester, New York, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

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