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

NCT ID: NCT00377104

Last Updated: 2013-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemotherapy)

Patients receive alvocidib 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.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

alvocidib

Given IV

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Diagnosis of 1 of the following:

• B-cell chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Must have received 1-3 prior therapies for CLL

• Completed therapy 2-12 months ago
• Prior therapy must have led to a partial response or greater
• No evidence of progressive disease
• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,000/mm³
• WBC ≤ 5,000/mm³
• Platelet count ≥ 50,000/mm³
• Cytopenia allowed
• Creatinine < 2.0 mg/dL
• Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
• AST ≤ 2 times normal (unless due to hemolysis)
• No secondary malignancy or other disease that would limit survival to < 2 years
• No history of inflammatory bowel disease unless inactive for > 2 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• See Disease Characteristics
• No other concurrent chemotherapy
• No concurrent radiotherapy
• No concurrent dexamethasone or other corticosteroid-based antiemetics
• No concurrent chronic corticosteroid therapy
• No other concurrent hormonal therapy except for the following:

• Steroids for new adrenal failure
• Hormones for nondisease-related conditions (e.g., insulin for diabetes)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leslie Andritsos

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

References

Awan FT, Jones JA, Maddocks K, Poi M, Grever MR, Johnson A, Byrd JC, Andritsos LA. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy. Ann Hematol. 2016 Jun;95(7):1137-43. doi: 10.1007/s00277-016-2683-1. Epub 2016 Apr 27.

Reference Type: DERIVED

PMID: 27118540 (View on PubMed)

Other Identifiers

OSU 05116

Identifier Type: -

Identifier Source: secondary_id

OSU-IRB-2006C0031

Identifier Type: -

Identifier Source: secondary_id

CDR0000501975

Identifier Type: -

Identifier Source: secondary_id

OSU-05116

Identifier Type: -

Identifier Source: secondary_id

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00161

Identifier Type: -

Identifier Source: org_study_id

NCT01645579

Identifier Type: -

Identifier Source: nct_alias