A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia
1) To determine whether there is an association between baseline mammalian target of
rapamycin (mTOR) activation paired with mTOR target inhibition post-treatment in leukemic
blasts and clinical response in patients with newly diagnosed acute myeloid leukemia (AML)
treated with sirolimus idarubicin/cytarabine.
1. To estimate the response rate of sirolimus idarubicin/cytarabine in patients with newly
diagnosed AML compared to historical data using idarubicin/cytarabine alone.
2. To determine the ability of oral sirolimus to inhibit mTOR in leukemic blasts.
3. To assess if mTOR pathway inhibition correlates with clinical response.
4. To collect further information on the safety, tolerability, and efficacy of sirolimus
in combination with idarubicin/cytarabine in patients with newly diagnosed AML.
5. To describe the progression-free survival and overall survival (1 year, 2 year and 5
year) of patients treated with sirolimus idarubicin/cytarabine.
Patients receive sirolimus orally (PO) once daily (QD) on days 1-10, idarubicin
intravenously (IV) over 3-5 minutes on days 4-6, and cytarabine IV continuously over 24
hours on days 4-10.
After completion of study treatment, patients are followed up every 3 months for 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in measurement of mTOR activation paired with mTOR target inhibition
The association between mTOR response and clinical response (complete or partial response) will be evaluated using the two-sided Fisher's exact test with alpha 0.05.
Baseline to day 4
Margaret Kasner, MD
Thomas Jefferson University
United States: Institutional Review Board
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|