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

This study has been completed.
Information provided by:
Fred Hutchinson Cancer Research Center Identifier:
First received: April 5, 2005
Last updated: September 20, 2010
Last verified: September 2010

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.

Condition Intervention Phase
Drug: cytarabine
Drug: idarubicin
Drug: pravastatin
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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

Study Start Date: January 2005
Study Completion Date: October 2005
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • Over 18

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified


  • Not specified


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


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


  • 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


  • 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


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00107523

United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Principal Investigator: Stephen H. Petersdorf, MD Fred Hutchinson Cancer Research Center
  More Information Identifier: NCT00107523     History of Changes
Other Study ID Numbers: 1945.00
CDR0000419678 ( Registry Identifier: PDQ )
Study First Received: April 5, 2005
Last Updated: September 20, 2010

Keywords provided by Fred Hutchinson Cancer Research Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors processed this record on May 25, 2017