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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00117156
• Other study ID #: 03-294
• Status: Completed
• Phase: Phase 2
• First received: June 30, 2005
• Last updated: July 28, 2016
• Start date: December 2003
• Est. completion date: January 2012

Study information

• Verified date: July 2016
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 2012
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Non-Hodgkin
• MALT Lymphoma

Intervention

Drug:
• Fludarabine

• Rituximab

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Rochester Cancer Center	Rochester	New York

Sponsors (6)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Beth Israel Deaconess Medical Center, Biogen, Genentech, Inc., Massachusetts General Hospital, University of Rochester

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 lymph — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No
Secondary	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	No