Clinical trial NCT00098371
Conditions: B-cell Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia
Sponsor: National Cancer Institute (NCI)
Start date: 2005-04-01; Completion date: 2012-11-01
Enrollment: 64 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial is studying how well flavopiridol works in treating patients with chronic lymphocytic leukemia or prolymphocytic leukemia. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the complete response (CR) and overall response rate (CR + Partial Response \[PR\]) of this regimen.

II. To assess the toxicity profile of this regimen. III. To examine response duration, progression-free survival and overall survival, following this treatment.

IV. To assess the pharmacokinetics of this novel schedule of administration.

SECONDARY OBJECTIVES:

I. To determine the influence of adverse prognostic factors including interphase cytogenetics, VH mutational status, ZAP-70 expression, CD38, and p53 mutational status with response to flavopiridol treatment.

II. To determine the influence of flavopiridol treatment on serial measurements of mcl-1 (mRNA and protein), HIF-1 (mRNA and protein), NF-kappaB activity, IkappaB, IkappaB phosphorylation, GSK-beta, and IL-6 down-stream targets.

III. To assess the relationship of drug induced apoptosis and mitochondrial perturbation of Chronic Lymphocytic Leukemia (CLL) cells in vitro and subsequent relationship to clinical response and tumor lysis in vivo.

IV. To examine cytokine levels (IL-6, IFN-gamma, TNF-alpha) during treatment with flavopiridol.

V. To assess pharmacokinetics (PK) to determine the variability of PK and PD analyses between treatment administrations and correlation with specific Single Nucleotide Polymorphisms (SNPs) potentially involved in flavopiridol disposition.

VI. To assess differences in diagnosis and relapse samples to investigate mechanisms of acquired flavopiridol resistance in primary CLL cells.

OUTLINE: This is an open-label study. Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22.

Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for \> 6 months after completion of treatment may receive 6 additional courses of flavopiridol.Patients are followed at 2 months and then every 3 months for 5 years.

Arms: arm 1: Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for \> 6 months after completion of treatment may receive 6 additional courses of flavopiridol.
Interventions: intervention 1: alvocidib
Intervention descriptions: intervention 1: None

Protocol documents: