A Phase II Study of Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Fludarabine
- Conditions
- Lymphoma, Non-Hodgkin
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 26
- Locations
- 4
- Primary Endpoint
- Objective Response Rate
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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%.
Investigators
Jennifer R. Brown, MD, PhD
Assistant Professor of Medicine
Dana-Farber Cancer Institute
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
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
Arms & Interventions
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.
Intervention: Fludarabine
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.
Intervention: Rituximab
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- 3.1-Year Progression-Free Survival(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(Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years)