A Pilot Trial With Subcutaneous Alemtuzumab and Oral Fludarabinephosphate for the Determination of Safety, Efficacy and Molecular Profiling for the Prediction of Response

Subcutaneous MabCampath® (Alemtuzumab) and Oral Fludara® (Fludarabinephosphate) for the Treatment of Refractory or Relapsed Chronic Lymphocytic Leukemia in 2nd or 3rd Line of Treatment: A Pilot Trial (FLUSALEM) for the Determination of Safety, Efficacy and Molecular Profiling for the Prediction of Response

Open label multicenter, two-step, non-randomized (pilot) study to analyze the safety of 4 cycles of 3-day 40mg/m2 oral fludarabine with simultaneous thrice weekly application of 30mg alemtuzumab s.c. in patients with B-CLL disease in 1st and 2nd relapse after any primary treatment or with disease refractory to any therapy in 1st or 2nd line (including Fludarabine, ). This regimen is preceded by an escalation phase with 3-10-30 mg of alemtuzumab s.c.

After the first phase (completed treatment of 7 patients) an interim analysis of safety and efficacy will be performed. In case of a sufficient risk benefit assessment followed by the enrollment of further 21 patients. Final analysis of safety and preliminary efficacy will be based on all patients enrolled.

Inclusion Criteria:

• Male or female patients with CD23+, CD5+, CD19+, light chain monoclonal B CLL
• 1st or 2nd relapse after fludarabine or any other primary treatment regimen or refractory to primary or secondary treatment (including fludarabine) and simultaneously indication for treatment according to the NCI Workshop Criteria 1996
• Age 19-75
• WHO performance score 0-2
• Informed consent given by the patient

Exclusion Criteria:

• HIV positive or positive for Hepatitis B or C
• active uncontrolled infection
• child bearing age without adequate control of fertility, pregnant or lactating women
• intolerance towards any ingredient of either oral fludarabine or alemtuzumab
• allergy against foreign proteins
• previous treatment with alemtuzumab
• treatment with an experimental drug within the previous 2 months
• second malignant disease (non CLL)
• CLL in transformation (Richter syndrome)
• decreased kidney-function with creatinine-clearance < 30ml/min
• severe concomitant diseases or major organ dysfunctions
• patients who are unable to comply with the requirements of the protocol