Pravastatin, Idarubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00107523

Purpose

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
Leukemia	Drug: cytarabine Drug: idarubicin Drug: pravastatin	Phase I

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:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Cholesterol Leukemia

Drug Information available for: Cytarabine hydrochloride Idarubicin hydrochloride Idarubicin Pravastatin Pravastatin sodium Cytarabine

U.S. FDA Resources

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 [ Designated as safety issue: No ]
Leukemia cell apoptosis [ Designated as safety issue: No ]
Maximum tolerated dose (MTD) of pravastatin [ Designated as safety issue: Yes ]
Maximal biological effect on cholesterol metabolism achieved with or without the MTD of pravastatin [ Designated as safety issue: Yes ]

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107523

Locations

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

Investigators

Principal Investigator:

Stephen H. Petersdorf, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00107523 History of Changes
Other Study ID Numbers:	1945.00, FHCRC-1945.00, MDA-2004-0185, CDR0000419678
Study First Received:	April 5, 2005
Last Updated:	September 20, 2010
Health Authority:	United States: Federal Government

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
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Pravastatin
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents

Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012