Clinical trial NCT00117156: Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
MALT Lymphoma
Keywords: Fludarabine
Rituximab
Marginal Zone Lymphoma
MALT lymphoma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: University of Rochester
name: Genentech, Inc.
name: Biogen
First posted: 2005-07-04
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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%.

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
* 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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Assessed after three- and six-cycles of therapy.
Secondary outcomes:
measure: 3.1-Year Progression-Free Survival
timeFrame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
measure: 3.1-Year Overall Survival
timeFrame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jennifer R. Brown, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 lymphomas. Br J Haematol. 2009 Jun;145(6):741-8. doi: 10.1111/j.1365-2141.2009.07677.x. Epub 2009 Mar 30.