Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

NCT ID: NCT00278330

Last Updated: 2013-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31

Brief Summary

This phase I trial is studying the side effects and best dose of flavopiridol when given together with vorinostat in treating patients with relapsed or refractory acute leukemia or chronic myelogenous leukemia or refractory anemia. Flavopiridol and vorinostat may cause leukemia cells to look more like normal cells, and to grow and spread more slowly. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving flavopiridol together with vorinostat may be an effective treatment for leukemia or refractory anemia.

Detailed Description

PRIMARY OBJECTIVE:

I. Determine recommended phase II doses for the combination of flavopiridol and vorinostat in patients with acute leukemia, chronic myelogenous leukemia in blast crisis, or refractory anemia with excess blasts-2.

SECONDARY OBJECTIVES:

I. Determine the safety, toxicity, tolerability, and maximum tolerated dose of this drug regimen.

II. Determine the pharmacodynamic and clinical anti-leukemic effects of this drug regimen.

III. Correlate leukemia gene expression patterns with response in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour on days 1-5 and oral vorinostat three times daily on days 1-14. Courses repeat every 21 days 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 6 patients experience dose-limiting toxicity.

Conditions

Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

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

Study Groups

Arm I

Patients will receive a 1-hour infusion of flavopiridol on 5 days in week 1 and vorinostat by mouth three times a day in weeks 1 and 2. Treatment may repeat every 3 weeks for as long as benefit is shown.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given by infusion

vorinostat

Intervention Type: DRUG

Given orally

Interventions

alvocidib

Given by infusion

Intervention Type: DRUG

vorinostat

Given orally

Intervention Type: DRUG

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza

Eligibility Criteria

Inclusion Criteria

• Diagnosis of one of the following:

• Relapsed or refractory acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or acute leukemia unclassifiable) following at least one prior systemic treatment
• Acute leukemia in a patient 60 years or older (no requirement for prior treatment)
• Acute leukemia that has evolved from a prior myelodysplastic syndrome
• Chronic myelogenous leukemia (CML) in blast crisis following prior imatinib mesylate therapy
• Refractory anemia with excess blasts-2 (RAEB-2)
• No known CNS leukemia
• ECOG performance status 0-2
• WBC < 50,000µL
• Hydroxyurea and/or leukaphereses may be used to lower WBC
• Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 50 mL/min
• Total bilirubin =< 2 times ULN
• AST/ALT =< 2.5 times ULN
• QTc interval =< 0.470 seconds
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No other condition that would preclude study participation
• At least 3 weeks since prior treatment (expect leukaphereses)
• No valproic acid therapy within the past 2 weeks
• No prior autologous or allogeneic bone marrow or stem cell transplantation
• No hydroxyurea use within the past 24 hours
• No concurrent treatment with other anti-cancer agents or investigational agents

• 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

Steven Grant

Role: PRINCIPAL_INVESTIGATOR

Massey Cancer Center

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Other Identifiers

MCC 6637

Identifier Type: -

Identifier Source: secondary_id

CDR0000656277

Identifier Type: -

Identifier Source: secondary_id

R21CA115260

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062490

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00077

Identifier Type: -

Identifier Source: org_study_id