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

Study Overview
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Brief Summary
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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
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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%.

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

Conditions
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Lymphoma, Non-Hodgkin, MALT Lymphoma

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine and Rituximab<br>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<br> <br> Drug: Rituximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Assessed after three- and six-cycles of therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fludarabine, Rituximab, Marginal Zone Lymphoma, MALT lymphoma