Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia in Partial Remission or Complete Remission

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. PURPOSE: This phase II trial is studying the side effects and how well alemtuzumab works in treating patients with B-cell chronic lymphocytic leukemia in partial remission or complete remission.

Detailed Description
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OBJECTIVES: Primary Determine the rate of achieving minimum residual disease (MRD) negativity after treatment with alemtuzumab in patients with B-cell chronic lymphocytic leukemia (B-CLL) who have low levels of MRD after conventional therapy or who relapse at an MRD level after a prior MRD-negative remission. Determine the safety of alemtuzumab in patients treated in the MRD-positive setting. Secondary Determine the clinical response in patients treated with this drug. Determine the time to MRD relapse in patients treated with this drug. Determine the overall survival of patients treated with this drug. Determine the effect of this drug when administered as consolidation/maintenance therapy on CD52 expression on CLL cells. Determine the safety and efficacy of repeated drug dosing required to achieve sustained MRD negativity in these patients. OUTLINE: This is a multicenter study. Observation: Patients with minimal residual disease (MRD)-negative status are observed every 4 weeks for 12 weeks and then every 12 weeks thereafter. If they become MRD-positive, then they are eligible for treatment. Treatment: Patients with MRD-positive status receive alemtuzumab subcutaneously or IV over 2 hours three times weekly for up to 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of 6 weeks of study therapy, patients are evaluated for response. Patients who remain MRD-positive and are responding to study therapy receive an additional 6 weeks of treatment. Patients who remain MRD-positive and show no significant improvement in the level of leukemic cells detected in their peripheral blood or bone marrow are removed from the study. Patients achieving MRD-negative remission are removed from study therapy and monitored for disease recurrence at an MRD level. If MRD-level relapse is confirmed in these patients, they may be retreated with alemtuzumab provided their initial response to therapy lasted for at least 6 months. Patients undergo collection of peripheral blood and bone marrow periodically during study for assessment of MRD by MRD flow cytometry, fluorescent in situ hybridization (FISH) analysis, somatic mutation analysis, and B-cell selection. After completion of study therapy, patients are followed periodically. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Official Title
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Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study

Conditions
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Leukemia

Intervention / Treatment
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* Biological: alemtuzumab
* Genetic: fluorescence in situ hybridization
* Genetic: mutation analysis
* Other: flow cytometry


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) meeting the following criterion: Confirmed by characteristic immunophenotype on peripheral blood flow cytometry In complete or partial remission after prior therapy for B-CLL No treatment failure after receiving prior alemtuzumab therapy Minimal residual disease (MRD) status meeting 1 of the following criteria: Detectable B-CLL MRD (i.e., MRD-positive) as shown by peripheral blood or bone marrow involvement Undetectable B-CLL MRD (i.e., MRD-negative remission) Lymph nodes < 2 cm in maximum diameter No persisting severe pancytopenia due to prior therapy rather than disease, as defined by the following criteria: Neutrophil count < 5,000/mm^3 Platelet count < 50,000/mm^3 No clinically progressive disease (i.e., peripheral blood B-cell count ≥ 5,000/mm³) No mantle cell lymphoma No CNS involvement with B-CLL PATIENT CHARACTERISTICS: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study therapy Creatinine < 2 times upper limit of normal (ULN)* Bilirubin < 2 times ULN* No known HIV positivity No concurrent active infection No history of anaphylaxis after exposure to rat or mouse-derived, complementary-determining region-grafted humanized monoclonal antibodies No other concurrent severe diseases or mental disorders No concurrent active secondary malignancy NOTE: *Unless secondary to direct infiltration of the liver by B-CLL or hemolysis PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior allogeneic stem cell transplantation Any other prior therapy allowed At least 6 months since completion of last therapy for B-CLL More than 6 weeks since prior investigational agents No other concurrent cytotoxic agents

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: alemtuzumab|nan|
|Genetic: fluorescence in situ hybridization|nan|
|Genetic: mutation analysis|nan|
|Other: flow cytometry|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy |  |  | 
| Rate of unacceptable toxicities |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall response (complete or partial response) |  |  | 
| Time to MRD relapse |  |  | 
| Overall survival |  |  | 
| Expression of CD52 on chronic lymphocytic leukemia cells |  |  | 
| Rate of re-achievement of MRD negativity after completion of alemtuzumab therapy |  |  | 
| Incidence of successful retreatment |  |  | 
| Toxicity from repeated therapy |  |  | 
| Length of interval between required treatments |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia