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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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B-cell Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Fludarabine phosphate
* Drug: Alemtuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overall study<br>The FLUSALEM protocol combines 4 cycles of oral fludarabine phosphate (40mg/m² d1-3; q 29d) and an intensive dose schedule of alemtuzumab (30mg sc.3 times weekly for 16 weeks) in an outpatient setting | Drug: Fludarabine phosphate<br>* orally, 40 mg/m2 d1-3 q4w, x4 cycles<br>* Other names: Fludara®;Drug: Alemtuzumab<br>* subcutaneous, starting dose 3 mg and escalation to 10 mg, then 30 mg, followed by 30 mg thrice weekly for 16 weeks in escalated dose<br>* Other names: MabCampath®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability |  | within the duration of study | 
| Complete and overall response rate |  | within the duration of study | 
| Infections grade III, IV |  | within the duration of study | 
| Rate of CMV reactivation |  | within the duration of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to retreatment |  | within duration of trial | 
| Overall survival |  | within duration of trial | 
| Response in lymphatic compartments |  | within duration of trial | 
| Molecular response/ immunologic MRD response |  | within duration of trial | 
| Quality of Life |  | within duration of trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-CLL, refractory, molecular profiling, alemtuzumab, fludarabinephosphate