SWOG S0919: A phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukemia (AML).

Leukemia Myelodysplasia and Transplantation
Session Type and Session Title: 
Poster Discussion Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 7028)
Anjali S. Advani, Shannon McDonough, Edward Copelan, Cheryl L. Willman, Deborah A. Mulford, Alan F. List, Mikkael A. Sekeres, Megan Othus, Harry P. Erba, Frederick R. Appelbaum; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; SWOG Statistical Center, Seattle, WA; Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC; University of New Mexico Cancer Center, Albuquerque, NM; University of Rochester Medical Center, Rochester, NY; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University of Alabama at Birmingham, Birmingham, AL; Fred Hutchinson Cancer Research Center, Seattle, WA

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Abstract Disclosures


Background: Inhibition of cholesterol synthesis and uptake sensitizes AML blasts to chemotherapy (Blood 104: 1816, 2004). A prior Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also reported an encouraging response rate (Blood 109: 2999, 2007). SWOG S0919 therefore evaluated the complete remission (CR) rate in a larger number of pts with relapsed AML treated with the pravastatin dose arrived at in the Phase 1 trial. Methods: Pts were treated at SWOG institutions from Aug 2009 through Nov 2012. Pravastatin was supplied by Bristol-Meyers Squibb. The protocol was approved by each institution’s review board. Eligibility: age ≥ 18 yrs, relapsed AML, cardiac ejection fraction ≥ 45%, CR/ CR with incomplete count recovery (CRi) following most recent chemotherapy lasting ≥ 3 months, no prior hematopoietic cell transplant. Treatment: oral pravastatin 1280 mg Days 1-8, idarubicin 12 mg/m2/d IV Days 4-6, and cytarabine 1.5 g/m2/d continuous IV infusion Days 4-7. Pts achieving a CR could receive 2 cycles of consolidation. CR and CRi were defined by IWG criteria. Fifty eligible pts were to be accrued. If ≥ 21 pts achieved CR or CRi, the regimen would be considered sufficiently effective (critical level = 4.8% if true CR rate = 30% and power of 90% if true CR rate = 50%). Results: The study closed to accrual on Nov 1, 2012 after meeting the defined criterion for a positive study. Thirty-six pts with a median age of 59 yr (range 23-78) were enrolled. Seventeen pts (47%) were male and the median WBC was 2800/ uL (range 700-110,600). The median time from initial dx to registration was 18 mo (range 5-136). Relapse status: 1st: 17 pts (47%), 2nd: 15 (42%), 3rd: 2 (5.5%), and 4th: 2 (5.5%). Eighteen pts have died, 3 during treatment. The response rate was 75% (95% CI 58-88%; 20 CR, 7 CRi); and the median overall survival was 10 mo. The p-value comparing 75% to 30% (null response rate) is 3.356 x 10-8. Duration of last CR (≤ 6 months) and prior high dose cytarabine exposure did not affect response to protocol treatment. Conclusions: The CR/ CRi in this relapsed population is encouraging. We plan to evaluate the efficacy of this regimen in higher-risk patients. Clinical trial information: NCT00840177.