NCT00735930

Lenalidomide and Alvocidib in Treating Patients With Relapsed or Refractory B-cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Phase 1 Trial of Flavopiridol in Combination With Lenalidomide in Patients With Relapsed or Refractory B-Cell CLL/SLL

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of lenalidomide when given together with alvocidib in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Lenalidomide may stop the growth of leukemia or lymphoma by blocking blood flow to the cancer. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with alvocidib may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of flavopiridol (alvocidib) in combination with lenalidomide in patients with relapsed or refractory B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). II. To define the specific toxicities and the dose limiting toxicity (DLT) of flavopiridol in combination with lenalidomide in the treatment of patients with relapsed or refractory CLL/SLL. SECONDARY OBJECTIVES: I. To assess preliminary efficacy of flavopiridol combined with lenalidomide in patients with relapsed/refractory CLL/SLL to justify future, rigorous phase II studies of the combination in CLL. II. To determine the pharmacokinetics of flavopiridol and lenalidomide alone and in combination in patients with CLL/SLL. III. To correlate select pre-treatment prognostic markers, including interphase cytogenetics with minimal residual disease, progression-free survival, response, and toxicity following combination therapy with flavopiridol and lenalidomide. IV. To determine patient cytokine expression profiles immediately pre-treatment, after flavopiridol dosing, and after combination flavopiridol and lenalidomide therapy to assess the impact of lenalidomide on flavopiridol induced cytokine release (interleukin \[IL\]-6). V. To assess if pre-treatment ex vivo and in vivo (day 1 and day 3 of lenalidomide) immune (B-cell, natural killer \[NK\] cell, and T-cell) activation correlates with response and toxicity of lenalidomide therapy. VI. To assess the in vivo effect of lenalidomide on flavopiridol on the modulation of selected intracellular pharmacodynamic targets including signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3), myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1), and other downstream IL-6 targets. OUTLINE: This is a dose-escalation study of lenalidomide. Patients receive alvocidib intravenously (IV) over 4.5 hours on days 1, 8, and 15 in course 1 followed by a week of rest. Beginning in course 2 and all subsequent courses, patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 and alvocidib IV over 4.5 hours on days 3, 10, and 17. Treatment repeats every 35 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 2 years.

Conditions

• Anemia
• Chronic Lymphocytic Leukemia
• Prolymphocytic Leukemia
• Recurrent Small Lymphocytic Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Thrombocytopenia

Interventions

Type	Name	Description
DRUG	Alvocidib Hydrochloride	Given IV
DRUG	Lenalidomide	Given PO
OTHER	Pharmacological Study	Correlative studies
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2008-08-01
• Primary completion: 2013-03-01
• Completion: 2014-11-01
• First posted: 2008-08-15
• Last updated: 2015-04-02

Locations

1 site across 1 country: United States