Rituximab Maintenance Therapy for Marginal Zone B-cell Lymphoma (MZL)

Study Overview
=================
Brief Summary
-----------------
The clinical efficacy of rituximab, a chimeric monoclonal antibody targeted toward the B-cell specific antigen CD20, was initially demonstrated in cases of follicular lymphoma (FL), but the use of this antibody has been extended over the last few years to the majority of subtypes of B-cell CD20 positive non-Hodgkin's lymphomas, with promising results thus far. In MZL, small numbers of case reports have chronicled the use of rituximab as a single agent or phase II trial combination with chemotherapeutic regimens. The results of the rituximab maintenance phase III trial demonstrated that patients with FL who continued to take rituximab monotherapy as a maintenance therapy after responding to an initial course of chemotherapy combined with or without rituximab experienced longer progression-free survival durations than did those who received no rituximab maintenance therapy. The efficacy of maintenance treatment after first-line induction treatment with R-chemotherapy was addressed in the international PRIMA (Primary Rituximab and Maintenance) study, which has enrolled 1,217 patients. The first results are eagerly awaited. Although MZL has better prognosis in TTP and OS than FL, both of them are classified as the same category of indolent lymphoma -characterized by frequent relapse and prolonged survival. According to the results of our survey, advanced stage MZL tends to be an indolent disease - characterized by prolonged survival with frequent relapses. Rituximab appears to contribute to better responses, but not in TTP. Thus, we should consider maintenance treatments for MZL patients, to extend their response duration.

Detailed Description
-----------------
no desire description

Official Title
-----------------
R-CVP Followed by Rituximab Maintenance Therapy for Patients With Advanced Marginal Zone B-cell Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Drug: rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed CD20 positive marginal zone B-cell lymphomas Ann Arbor stage III or IV No prior chemotherapy or radiotherapy for advanced stage MZL Tumor response after 8th cycles of R-CVP CTx ≥ SD (Stable disease) Performance status (ECOG) ≤ 2 age ≥ 20 At least one or more bidimensionally measurable lesion(s): ≥ 2 cm by conventional CT/ ≥ 1 cm by spiral CT/ skin lesion (photographs should be taken) ≥ 2 cm/ measurable lesion by physical examination ≥ 2 cm Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L) Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value / Bilirubin < 1.5 X upper normal value /Alkaline phosphatase < 5 X upper normal value Adequate BM functions:ANC > 1500/uL and platelet > 75,000/uL and Hemoglobin > 9.0 g/dL unless abnormalities are due to bone marrow involvement by lymphoma Informed consent Exclusion Criteria: Other subtypes NHL than MZL Large cell component >10% Tumor response after 8th cycles CTx = PD (Progression disease) Central nervous system (CNS) metastasis Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions i. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry ii. History of significant neurologic or psychiatric disorders including dementia or seizures iii. Active uncontrolled infection (viral, bacterial or fungal infection) iv. Other serious medical illnesses Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies) Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>rituximab 375mg/m2, every 8 weeks, 12 times | Drug: rituximab<br>* rituximab 375mg/m2, every 8 weeks, 12 times<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year progression free survival | Historic 3 year progression free survival rate was 60 %, expected difference 20%, power 0.80, significance 0.05 and drop rate=0.1. | 3 years after last patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years after last patients enrollment | 
| toxicity |  | during the Rituximab maintenance treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lymphoma, B-Cell, Marginal Zone, Rituximab