Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

All screening activities are to be completed within 28 days prior to Cycle 1, Day 1.

Baseline evaluations must occur within 4 weeks of the first dose of treatment. Test results
must be obtained and reviewed and the patient's continued eligibility for the study
confirmed before alemtuzumab administration on Day 1 of Cycle 1.

Patients will be followed until irreversible dose limiting toxicity occurs, disease
progression, administration of therapy outside the context of this clinical trial, or death.

The primary safety endpoint is the incidence of dose limiting toxicity up to 5 weeks
following the last alemtuzumab dose. Safety assessments will consist of monitoring and
recording of all adverse events, physical examinations, measurement of vital signs,
laboratory analyses, and tumor assessments.

The dose of bendamustine is derived from a Phase I/II clinical trial in a population of
patients with advanced CLL that determined the maximally tolerated dose 29. The dose of
alemtuzumab is derived from reports of an excellent safety profile with low doses
administered over a long period of time. The dose of alemtuzumab will not be escalated
higher than 30mg thrice weekly since this is the standard dose of alemtuzumab in clinical
practice. Treatment will be administered as follows:

Bendamustine 70 mg/m2 IV Day 8 and 9 every 28 days for 6 courses of therapy.

Patients will be premedicated with palonosetron 0.25 mg IV prior to bendamustine.

Alemtuzumab will be dose escalated as follows:

Cohort 1: 10mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 every 28
days for 3 courses of therapy.

Cohort 2: 20mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 every 28
days for 3 courses of therapy.

Cohort 3: 30mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 every 28
days for 3 courses of therapy.