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

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.

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