Pravastatin, Idarubicin, and Cytarabine in Treating Patients With Acute Myeloid 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 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|
- 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|
- 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.
|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|
|Principal Investigator:||Stephen H. Petersdorf, MD||Fred Hutchinson Cancer Research Center|