Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Concomitant Evaluation of Safety and Efficacy.

The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen.

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study in patients with previously untreated CD20-positive CLL. Phase I of the study will evaluate the maximal tolerated lenalidomide dose level in combination with fludarabine/rituximab chemoimmunotherapy in 10 patients. Phase II will determine efficacy using the combination in the previously defined maximal tolerated dose. Both phases will be followed by a maintenance phase evaluating the tolerability and possibility to further improve response quality.

Inclusion Criteria:

• B-CLL (CD23+, CD5+, CD19+, CD20+)
• Treatment indication according to NCI criteria
• Age >= 18 yrs
• No previous treatment of CLL by chemo-, radio- or immunotherapy
• Life expectancy > 6 months
• Written informed consent
• Women of non-childbearing potential or women of childbearing potential and men using effective contraception

Exclusion Criteria:

• Active bacterial, viral or fungal infection
• Positivity for HIV, Hepatitis B or C
• Reduce organ functions and bone marrow dysfunction not due to CLL
• Creatinine clearance below 30 ml/min
• Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment
• Patients with a history of severe cardiac disease
• Other known co-morbidity with the potential to dominate survival
• Transformation to aggressive B-cell malignancy
• Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs
• Pregnant or breast-feeding women
• Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent