Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas

Study Overview
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Brief Summary
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The purpose of this study is to determine if an extended maintenance therapy with Rituximab in follicular and a maintenance therapy in other indolent and mantle cell lymphomas has advantages compared to a shorter or no maintenance therapy.

Detailed Description
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Results from several randomised studies show a clinical benefit of a maintenance therapy with rituximab in follicular lymphomas. The advantage of a maintenance therapy in other indolent and mantle cell lymphomas is - due to the lower incidence of these diseases- not well investigated. This study tries to determine the significance of an extended maintenance therapy with rituximab in follicular lymphomas and the significance of a maintenance therapy other indolent and mantle cell lymphomas compared to observation.

Official Title
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Prospective Randomized Multicenter Study in First-line Treatment of Advanced progredIeNT Follicular And Other IndoleNt and Mantle Cell Lymphomas

Conditions
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Follicular Lymphomas, Immunocytomas, Marginal Zone Lymphomas, Mantle-Cell Lymphomas, Lymphocytic Lymphoma, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Rituximab / observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histological verified CD20-positive B-Cell-Lymphoma of the following entities: Follicular Lymphoma Grade 1 and 2 Lymphoplasmocytic lymphoma / Immunocytoma (Morbus Waldenström) and small cell lymphocytic lymphoma (CLL without leukemic hemogram) Marginal zone lymphoma, nodal and extra nodal Mantle cell lymphoma No prior therapy with cytotoxics, interferon or monoclonal antibodies Need for therapy, except mantle cell lymphomas Stadium III or IV or Stadium with II bulky disease (> 7 cm diameter, or 3 lesions > 5 cm) General condition WHO 0-2 Age min. 18 years, max. 80 years Negative pregnancy test, contraceptives mandatory for women of child-bearing age Actual histology, not older than 6 months required Written informed consent Exclusion Criteria: Patients not meeting the inclusion criteria above Possibility of a primary radiation therapy with curative intention Pretreatment, except a single, localized radiation therapy (radiation field not larger than 2 adjacent lymph node regions) Co-morbidities, excluding a therapy according to the protocol: severe, medicinal not adjustable hypertension severe limited capacity of the heart (NYHA III or IV), the lung (WHO-Grade III or IV), the liver and kidneys (creatinin > 2 mg/dl, GOT and GPT or bilirubin 3 x ULN), except if caused by lymphoma severe, medicinal not adjustable diabetes mellitus active autoimmune disease active infection, requiring antibiotic therapy Patients with proven HIV-infection Active replicating hepatitis-Infection Severe psychiatric diseases Lacking or anticipated non-compliance Known hypersensitivity against the active components or additives or mouse- proteins Pregnant or nursing women Patients with a secondary malignancy or malignant disease in his history if, curative surgery can not be doubtless assured .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Follicular Lymphomas: Rituximab 375 mg/m² for additional 2 years after 2 years of standard maintainance All other lymphomas: Rituximab 375 mg/m² for 2 years as maintainance. From 2014 only Morbus Waldenstroem: Rituximab 1.400 mg absolute s. c. injection | Drug: Rituximab<br>* Follicular Lymphomas: induction therapy with bendamustine + rituximab. If CR or PR: Maintenance therapy with rituximab every 2 months for 4 years Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years<br>* Other names: Rituxan(R);|
| Active Comparator: Standard<br>Rituximab / Observation | Drug: Rituximab / observation<br>* Follicular Lymphomas:induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years (standard) Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: observation (standard)<br>* Other names: Rituxan(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Time from randomization until progress or death of any course | 5 years and ongoing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate and duration; event free-, progression free-, disease free- and over all survival | Time from randomization until treatment failure due to progression or not achieving any remission; time from achievin CR or PR until progression or relapse | 5 years and ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bendamustine, Rituximab, Significance of maintenance therapy, Efficacy and safety