Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
This phase I/II trial studies the side effects and best dose of flavopiridol in treating
 patients with previously treated chronic lymphocytic leukemia or lymphocytic lymphoma. Drugs
 used in chemotherapy such as flavopiridol work in different ways to stop cancer cells from
 dividing so they stop growing or die.
PRIMARY OBJECTIVES:

 I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of
 flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once
 weekly for 4 consecutive weeks every 6 weeks.

 II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30
 mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in
 patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.

 III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol
 administered in this schedule.

 SECONDARY OBJECTIVES:

 I. To determine the complete response (CR) and overall response rate (CR + PR) of
 flavopiridol in patients with previously-treated CLL administered as a 30 minute loading dose
 followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.

 OUTLINE: This is a dose-escalation study.

 Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour
 infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the
 absence of unacceptable toxicity or disease progression.

 Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated
 dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
 of 6 patients experience dose-limiting toxicity. After the MTD is determined, 12 additional
 patients are accrued and treated as above at the recommended phase II dose.

 After completion of study treatment, patients are followed at 2 months and then every 3
 months for 2 years.
Inclusion Criteria:

 -  Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma,
 including Waldenstrom's macroglobulinemia, as indicated by the following:

 -  Massive or progressive splenomegaly and/or lymphadenopathy

 -  Anemia (hemoglobin less than 11 g/dL) or thrombocytopenia (platelet count less
 than 100,000/mm^3)

 -  Weight loss of more than 10% within the past 6 months

 -  Grade 2 or 3 fatigue

 -  Fevers greater than 100.5º C or night sweats for more than 2 weeks with no
 evidence of infection

 -  Progressive lymphocytosis with an increase of more than 50% over a 2-month period
 or anticipated doubling time of less than 6 months

 -  Received at least 1 prior therapy for CLL

 -  Performance status - ECOG (Eastern Cooperative Oncology Group) 0-2

 -  See Disease Characteristics

 -  WBC (white blood count) less than 200,000/mm^3

 -  Bilirubin no greater than 1.5 times normal (unless due to Gilbert's disease or any of
 the conditions stated below)*

 -  AST (aspartate aminotransferase) no greater than 2 times normal*

 -  Creatinine no greater than 2.0 mg/dL

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  No other malignancy that would limit survival to less than 2 years

 -  No history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
 unless inactive for more than 2 years

 -  No psychiatric condition that would preclude compliance with treatment or giving
 informed consent

 -  No other concurrent chemotherapy

 -  No concurrent chronic corticosteroids

 -  No concurrent hormonal therapy except steroids for new adrenal failure or hormonal
 agents for nondisease-related conditions (e.g., insulin for diabetes)

 -  No concurrent dexamethasone or other corticosteroid-based antiemetics

 -  No concurrent radiotherapy