NCT00377104

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, 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. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. SECONDARY OBJECTIVES: I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients. II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol. OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. 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. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin \[IL\]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V\_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined. After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.

Conditions

• B-cell Chronic Lymphocytic Leukemia
• Contiguous Stage II Small Lymphocytic Lymphoma
• Noncontiguous Stage II Small Lymphocytic Lymphoma
• Stage I Chronic Lymphocytic Leukemia
• Stage I Small Lymphocytic Lymphoma
• Stage II Chronic Lymphocytic Leukemia
• Stage III Chronic Lymphocytic Leukemia
• Stage III Small Lymphocytic Lymphoma
• Stage IV Chronic Lymphocytic Leukemia
• Stage IV Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	alvocidib	Given IV
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2006-09-01
• Primary completion: 2012-11-01
• First posted: 2006-09-15
• Last updated: 2013-07-02

Locations

1 site across 1 country: United States