Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

OBJECTIVES: Determine the complete and partial response rate to flavopiridol in patients with fludarabine-refractory chronic lymphocytic leukemia.

Assess the toxicity profile of this treatment in these patients. Examine progression-free survival and overall survival following this treatment in these patients.

Determine the effects of flavopiridol on normal T-cell subsets and immunoglobulin levels in these patients.

OUTLINE: This is an open label, multicenter study.

Patients registered before 9/15/2000 receive flavopiridol IV continuously on days 1-3. Treatment repeats every 14 days for a total of 12 courses in the absence of disease progression or unacceptable toxicity.

Patients registered after 9/15/2000 receive flavopiridol IV over 1 hour daily on days 1-3. Treatment repeats every 3 weeks for a total of 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for the first year and then every 6 months for 5 years.

Inclusion criteria

• Histologically diagnosed intermediate risk (stage I or II) or high risk (stage III or IV) refractory B-cell chronic lymphocytic leukemia
• Intermediate risk group must have evidence of active disease as shown by at least one of the following:

• Massive or progressive splenomegaly and/or lymphadenopathy
• Weight loss of greater than 10% in the last 6 months
• CALGB grade 2-4 fatigue
• Fevers greater than 100.5 degree Fahrenheit OR night sweats for greater than2 weeks without evidence of infection
• Progressive lymphocytosis with an increase greater than 50% over a 2 month period or an anticipated doubling time of less than 6 months
• Refractory to fludarabine treatment OR relapsed within 6 months of fludarabine
• Lymphocytosis greater than 5000/mm3 at some time during disease
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Creatinine no greater than 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No more than 1 prior nonradiolabeled antibody treatment (e.g., Campath-1H or rituximab)
• At least 1, but no more than 3, prior chemotherapy regimens
• At least 1 prior chemotherapy regimen comprising fludarabine
• No other concurrent chemotherapy
• No concurrent chronic use of oral corticosteroids
• No concurrent hormone therapy except for non-disease related conditions
• No concurrent dexamethasone or other corticosteroid-based antiemetics
• No concurrent palliative radiotherapy