Alemtuzumab/Fludarabine for Relapsed/Refractory B-cell Chronic Lymphocytic Leukemia (B-CLL)

Study Overview
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Brief Summary
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This is a multi-center, Phase II, open label trial evaluating the efficacy and safety of alemtuzumab and fludarabine in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) patients who have received at least one prior therapy. Treatments will be administered on a 28-day cycle for 4-6 cycles, with an evaluation during Cycle 4 to permit re-staging. Alemtuzumab and fludarabine will be administered on Days 1-5 of each cycle. Patients will be assessed for response at the time of re-staging at Cycle 4 and at the end of Cycle 6. At the time of the re-staging, patients achieving a Partial Remission (PR) or Stable Disease (SD) will be given an additional 2 cycles of treatment and patients demonstrating presumptive signs of a Complete Remission (CR) will receive no further treatment but will be followed for response.

Detailed Description
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As of April, 2011 Bayer transferred this record to Genzyme. Genzyme is now the sponsor of this trial. NOTE: This study has previously been posted by Berlex, Inc. Berlex, Inc. has been renamed to Bayer HealthCare Pharmaceuticals, Inc.

Official Title
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Phase II Study Using Alemtuzumab Combined With Fludarabine for the Treatment of Relapsed/Refractory B-cell Chronic Lymphocytic Leukemia (B-CLL)

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: Alemtuzumab plus Fludarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have confirmed B-CLL. Patients must have received at least one prior therapy and must require treatment for active disease Exclusion Criteria: Treatment with any anti-cancer agents (chemotherapies, monoclonal antibodies, etc) within 4 weeks of start of study. History of significant allergic reaction to antibody therapies that required discontinuation of antibody therapy History of human immunodeficiency virus (HIV) positivity. Active infection requiring treatment Pregnancy or lactation Other severe, concurrent diseases or mental disorders Central nervous system involvement of chronic lymphocytic leukemia (CLL)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab plus Fludarabine<br>Alemtuzumab (Campath) 30mg subcutaneous (SC) plus Fludarabine (Fludara) 25mg/m² intravenous (IV), Days 1-5 every 28 days. | Drug: Alemtuzumab plus Fludarabine<br>* Alemtuzumab (Campath) 30mg subcutaneous (SC) plus Fludarabine (Fludara) 25mg/m² intravenous (IV), Days 1-5 every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) | Participants evaluated for therapeutic clinical response according to National Cancer Institute (NCI) response criteria, 28 days after 4 or 6 treatment cycles. Response confirmation involved bone marrow biopsy and aspirate performed 2 months after final treatment. CR requires for at least 2 months: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count (CBC); confirmed by bone marrow aspirate and biopsy 2 months later with lymphocytes <30% of nucleated cells and procedure repeated in 4 weeks if hypocellular. | 28 days after last cycle with confirmation 2 months later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response (OR) | Participant had either complete response (CR) or partial response (PR) at 28 days after last treatment cycle (date of OR) and at Months 2 follow-up. PR requires for at least 2 months: 50% decrease from Baseline in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence or absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin, or 50% improvement from Baseline for these parameters without transfusions, nodular CR or persistent anemia/thrombocytopenia unrelated to disease. | 28 days after last cycle with confirmation 2 months later | 
| Overall Survival (OS) | Percentage of participants alive 1 year after the first dose date, described as Kaplan-Meier estimate at 1 year | 1 year after start of treatment | 
| Progression-free Survival (PFS) | Percentage of participants who survived progression-free at 1 year, described as Kaplan-Meier estimate at 1 year | 1 year after start of treatment | 
| Percentage of Participants With Overall Response at Different Observation Times | Participant had either complete response (CR) or partial response (PR) at different observation times (after 90 days; after 180 days; after 270 days). PR requires for at least 2 months: 50% decrease from Baseline in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence or absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin, or 50% improvement from Baseline for these parameters without transfusions, nodular CR or persistent anemia/thrombocytopenia unrelated to disease. | from first date of confirmed response until relapse, or death, or study data cutoff date, whichever is earlier | 
| Number of Participants With Minimal Residual Disease (MRD) | Presence of MRD was assessed by laboratory testing of molecular responses in blood and bone marrow samples. | When CR is confirmed |