Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab

Study Overview
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Brief Summary
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The study addresses the question if a therapy with bendamustine plus rituximab is comparable (non inferior) with the well-tried combination of fludarabine plus rituximab with regard to event free survival (EFS) in recurrent low malignant Non-Hodgkin and mantle cell lymphomas.

Official Title
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Prospective Randomised Multicenter Study for Therapy Optimization of Recurrent, Progressive Low Grade Non-Hodgkin Lymphomas and Mantle Cell Lymphomas

Conditions
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Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Bendamustine plus Rituximab
* Drug: Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histological verified CD20-positive B-Cell-Lymphomas of the following entities: Follicular lymphoma grade 1 and 2 Immunocytoma and lymphoplasmocytic lymphoma Marginal zone lymphoma, nodal and generalised Mantle cell lymphoma lymphocytic lymphoma (CLL without leucaemic characteristics) non-specified/classified lymphomas of low malignancy Recurrent disease (remission duration minimum 3 months), independent of type or quantity of prior therapies, except of Rituximab containing regimens, or if remission duration is > 1 year after Rituximab containing regimen, or refractory to prior therapy (progression under therapy or during 3 months after completion), except refractory disease to purin analogs or Bendamustine Need for therapy, except mantle cell lymphomas Stadium II (bulky disease, 7.5 cm), II or IV Written informed consent Performance status WHO 0-2 Histology not older than 6 months Exclusion Criteria: Patients not establishing all above mentioned prerequisites Option of a primary, potentially curative radiation therapy Patients refractory to Rituximab containing regimens Comorbidities excluding a study conform therapy: heart attack during the last 6 months severe, medicinal not adjustable hypertonia severe functional defects of the heart (NYHA III or IV) lung (WHO grade III or IV) liver or kidney (creatinine > 2 mg/dl, GOT + GPT or bilirubin 3 x ULN, except caused by lymphoma Active auto immunohemolytic anemia (AIHA) HIV positive patients Active hepatitis infection Severe psychiatric diseases No compliance or non-compliance to be expected Pregnant or breast feeding women Anamnestic malignancies or secondary malignancies, not proven Cured/curable by surgery

Ages Eligible for Study
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Minimum Age: 18 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: Bendamustine plus Rituximab<br>Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w | Drug: Bendamustine plus Rituximab<br>* Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles<br>|
| Active Comparator: Fludarabine plus Rituximab<br>Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w | Drug: Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w<br>* Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival | From date of randomization until the date of first documented progression, date of detection of a secondary malignancy or date of death from any cause, whichever came first. Minimum 1 year | Observation till event or death, minimum 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission Rates | From date of randomization until the date of first documented progression, date of detection of a secondary malignancy or date of death from any cause, whichever came first. Minimum 1 year | Observation till event or death, minimum 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Event free survival, Remission rates, Toxicity, Overall survival, Efficiency costs, Recurrent low grade