Trial Information

Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

This study proposes to combine alemtuzumab, which effectively treats peripheral blood and
bone marrow disease in CLL, with rituximab, which has activity in lymph node disease, in a
streamlined and convenient administration schedule. Preclinical data support synergistic
interaction of the two. The primary objectives are (1) to determine the overall and
complete response (CR) rate in patients with relapsed CLL and to determine the safety of the
combination, and (2) the safety of higher doses of alemtuzumab at less frequent intervals.
Secondary objectives are (1) to describe the duration of response, progression-free
survival, and overall survival in patients not proceeding to allo transplant, (2) to
determine the improvement in overall and complete response associated with administration of
a 2nd eight week course of therapy, and (3) to assess minimal residual disease in certain
patients and to correlate those results with survival. If at least 16 responses are
observed among 35 patients, then the treatment will be considered promising.

The development of antibody therapies has held promise for CLL, since CLL therapies have
been palliative, with no established therapy shown to improve survival. Studies have
suggested that in contrast to what is seen with fludarabine and alkylating agents, response
rates to alemtuzumab are maintained in CLL subjects with P53 mutations. Tolerability of
rituximab and its major activity in nodes make it an attractive candidate for combination
with alemtuzumab.

This is a single center (DF/HCC), single arm, multi cohort, phase I study, with treatment on
an outpatient basis. If the initial alemtuzumab dose of 30 mg sc d1, 3,and 5 is tolerated,
there will be dose escalations in cohorts of 3, up to 90 mg d1 per week. Following
determination of a maximum tolerated dose, accrual of all remaining patients will occur at
that dose. Subjects will be restaged after 8 weeks of therapy, and may proceed to
transplant. If deriving benefit, but not in CR, subjects may receive another 8 weeks of
therapy.