Trial Information

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

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.