Pravastatin, Idarubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia

NCT ID: NCT00107523

Last Updated: 2010-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2005-10-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pravastatin may help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving pravastatin together with idarubicin and cytarabine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of pravastatin when given together with idarubicin and cytarabine in treating patients with acute myeloid leukemia.

Detailed Description

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OBJECTIVES:

* Determine the biological efficacy of pravastatin in leukemia cells, in terms of measuring surrogate endpoints, including cellular cholesterol, messenger RNA encoding cholesterol synthesis, cholesterol import regulators, and specific protein farnesylation, in patients with acute myeloid leukemia.
* Determine whether increasing doses of pravastatin, when administered with idarubicin and high-dose cytarabine, produce increased apoptosis in leukemia cells of these patients.
* Determine the maximum tolerated dose (MTD) of pravastatin when administered with idarubicin and high-dose cytarabine in these patients.
* Determine whether the MTD of pravastatin is required to achieve the maximal biological effect on cholesterol metabolism in leukemia cells of these patients.

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

Patients receive oral pravastatin once daily on days 1-8, idarubicin IV over 30 minutes on days 4-6, and high-dose cytarabine IV continuously on days 4-7. Treatment repeats every 28-42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) may receive additional treatment with the same doses of study drugs over fewer days. These patients receive oral pravastatin once daily on days 1-6 and idarubicin IV over 30 minutes and high-dose cytarabine IV continuously on days 4 and 5. Patients experiencing disease response with severe side effects may receive additional treatment at a lower dose of the study drug causing the side effects.

Cohorts of 3 patients receive escalating doses of pravastatin until the maximum tolerated dose (MTD)\* is determined or a predetermined maximum dose is reached.

NOTE: \*Patients achieving a CR with a dose of pravastatin that is subsequently determined to be above the MTD receive pravastatin at the MTD for all subsequent courses.

After completion of study treatment, patients are followed at least every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 2 years.

Conditions

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Leukemia

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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cytarabine

Intervention Type DRUG

idarubicin

Intervention Type DRUG

pravastatin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* No cardiac contraindication to idarubicin

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative
* No uncontrolled or life threatening infection
* No known intolerance to study drugs
* Must be able to safely tolerate the 3-day delay between the start of pravastatin and the start of chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* No other concurrent HMG-CoAR inhibitors, including any of the following:

* Atorvastatin
* Fluvastatin
* Lovastatin
* Rosuvastatin
* Simvastatin
* No concurrent non-HMG-CoAR inhibitors to lower cholesterol
* No concurrent use of any of the following medications:

* Bezafibrate
* Clofibrate
* Fenofibrate
* Gemfibrozil
* Cholestipol
* Cholestyramine resin
* Colesevelam
* Ezetimibe
* Biphenabid
* Niacin
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Principal Investigators

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Stephen H. Petersdorf, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

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M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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FHCRC-1945.00

Identifier Type: -

Identifier Source: secondary_id

MDA-2004-0185

Identifier Type: -

Identifier Source: secondary_id

CDR0000419678

Identifier Type: REGISTRY

Identifier Source: secondary_id

1945.00

Identifier Type: -

Identifier Source: org_study_id