A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL

Inclusion Criteria:

- Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic
leukemia* (PLL) arising from CLL

- Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point
since initial diagnosis of CLL

- Patients must have B-cells that co-express CD5 with CD19 or CD20

- Patients who do not have dim sIg or CD23 expression on their leukemia cells
should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle
cell lymphoma

- To be considered high risk, patients must meet the following criteria:

- At least 1 of the following:

- 17p deletion

- 11q deletion

- Un-mutated IgV_H (≥ 98% homology)

- Age > 70 years

- B_2M > 4

- AND at least 1 of the following:

- Progressive or marked splenomegaly and/or lymphadenopathy

- Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets <
100,000/mm^3)

- Weight loss exceeding 10% of body weight over preceding 6 months

- NCI grade 2 or 3 fatigue

- Fevers > 100.5° F or night sweats for > 2 weeks without evidence of
infection

- Progressive lymphocytosis, with an increase exceeding 50% over a 2-month
period or a doubling time of < 6 months

- No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for
new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for
diabetes)

- No requirement for chronic corticosteroids

- ECOG performance status 0-2

- Creatinine ≤ 2.0 mg/dL

- Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease
infiltration of the liver

- AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No secondary or other malignancy that will limit survival to < 2 years

- No uncontrolled concurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study
requirements

- No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication

- No active hepatitis B infection

- No known G6PD deficiency

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used
in this study

- No prior alvocidib

- No prior purine analog therapy

- No more than 1 prior treatment with a biologic or alkylating agent

- No other concurrent investigational agents