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SWOG S0919: A phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukemia (AML).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by A. S. Advani:
- Meeting: 2011 ASCO Annual Meeting | Abstract No: 6628
Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response (CR) plus complete marrow response (mCR) of greater than 50% in refractory relapse (R-R) acute lymphocytic leukemia (ALL).Meeting: 2011 ASCO Annual Meeting | Abstract No: 6507