Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia in Partial Remission or Complete Remission
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.
|Leukemia||Biological: alemtuzumab Genetic: fluorescence in situ hybridization Genetic: mutation analysis Other: flow cytometry||Phase 2|
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study|
- Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy
- Rate of unacceptable toxicities
- 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
|Study Start Date:||December 2006|
|Study Completion Date:||February 2008|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00458523
|Kent and Canterbury Hospital|
|Canterbury, England, United Kingdom, CT1 3NG|
|Leeds General Infirmary|
|Leeds, England, United Kingdom, LS1 3EX|
|Study Chair:||Peter Hillmen, MD||Leeds General Infirmary|