Pravastatin, Idarubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia
Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: cytarabine (Drug); idarubicin (Drug); pravastatin (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Fred Hutchinson Cancer Research Center Official(s) and/or principal investigator(s): Stephen H. Petersdorf, MD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Summary
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.
Clinical Details
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
Study design: Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Biological efficacy by measuring surrogate end-points, including cellular cholesterol, messenger RNAs encoding cholesterol synthesis and cholesterol import regulators, and specific protein farnesylationLeukemia cell apoptosis Maximum tolerated dose (MTD) of pravastatin Maximal biological effect on cholesterol metabolism achieved with or without the MTD of pravastatin
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: January 2005
Last updated: September 20, 2010
|