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

September 20, 2010 updated by: Fred Hutchinson Cancer Center

A Phase I Trial Evaluating the Effect of the Addition of HMGCoA-Reductase Inhibition With Pravastatin to Salvage Chemotherapy Idarubicin-HDAC in Patients With Relapsed or Refractory Acute Myelogenous Leukemia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M.D. Anderson Cancer Center at University of Texas
    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:

    • Newly diagnosed disease (MDACC patients only)
    • In first or second relapse AND scheduled to receive first salvage therapy
    • Primary refractory disease after prior induction therapy for newly diagnosed disease

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • AST or ALT ≤ 2 times normal
  • Alkaline phosphatase ≤ 2 times normal
  • Bilirubin < 2.0 mg/dL
  • No acute or chronic hepatic impairment

Renal

  • Creatinine < 1.5 times normal (unless secondary to acute myeloid leukemia)

Cardiovascular

  • Ejection fraction (EF) ≥ 45% by MUGA or 2-D echocardiogram

    • Patients who have an EF < 45% OR cardiac symptoms must be evaluated and cleared by cardiology to be eligible for study entry
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Biological efficacy by measuring surrogate end-points, including cellular cholesterol, messenger RNAs encoding cholesterol synthesis and cholesterol import regulators, and specific protein farnesylation
Leukemia cell apoptosis
Maximum tolerated dose (MTD) of pravastatin
Maximal biological effect on cholesterol metabolism achieved with or without the MTD of pravastatin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2005

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 5, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 5, 2005

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2010

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2010

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1945.00
  • FHCRC-1945.00
  • MDA-2004-0185
  • CDR0000419678 (REGISTRY: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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