Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab

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

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.

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