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

• Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy [ Designated as safety issue: No ]
  
• Rate of unacceptable toxicities [ Designated as safety issue: Yes ]
  

• Rate of overall response (complete or partial response) [ Designated as safety issue: No ]
  
• Time to MRD relapse [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Expression of CD52 on chronic lymphocytic leukemia cells [ Designated as safety issue: No ]
  
• Rate of re-achievement of MRD negativity after completion of alemtuzumab therapy [ Designated as safety issue: No ]
  
• Incidence of successful retreatment [ Designated as safety issue: No ]
  
• Toxicity from repeated therapy [ Designated as safety issue: Yes ]
  
• Length of interval between required treatments [ Designated as safety issue: No ]
  

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.