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

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

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.

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%.

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