Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Untreated Adult Acute Myeloid Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia|
- Change in measurement of mTOR activation paired with mTOR target inhibition [ Time Frame: Baseline to day 4 ] [ Designated as safety issue: No ]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.
- Overall survival [ Time Frame: 1 year, 2 years, 5 years ] [ Designated as safety issue: No ]Will be evaluated using the Kaplan-Meier method stratified by mTOR response. Log rank test will be used to compare the overall survival in patients with and without mTOR response. Based on the estimated survival curves, the 1-year, 2-year, and 5-year survival rates will be computed with the corresponding 95% confidence intervals.
- Progression free survival [ Time Frame: 1 year, 2 years, 5 years ] [ Designated as safety issue: No ]Based on the estimated survival curves, the 1-year, 2-year, and 5-year survival rates will be computed with the corresponding 95% confidence intervals.
- Incidence of toxicities, graded according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 4.0 guidelines [ Time Frame: Up to 45 days ] [ Designated as safety issue: Yes ]Safety data analysis is descriptive. All estimates of adverse events rates will be presented with corresponding confidence intervals using the exact method.
- Response defined as patients achieving a complete remission (CR), complete response in absence of total platelet recovery (CRp), or partial remission (PR) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Proportions of complete response and partial response with be computed separately in patients with and without mTOR response and presented with corresponding exact binomial 95% confidence intervals.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sirolimus, idarubicin, cytarabine)
Patients receive sirolimus PO QD on days 1-10, idarubicin IV over 3-5 minutes on days 4-6, and cytarabine IV continuously over 24 hours on days 4-10.
Other Names:Drug: Idarubicin
Other Names:Drug: Cytarabine
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.
- To estimate the response rate of sirolimus idarubicin/cytarabine in patients with newly diagnosed AML compared to historical data using idarubicin/cytarabine alone.
- To determine the ability of oral sirolimus to inhibit mTOR in leukemic blasts.
- To assess if mTOR pathway inhibition correlates with clinical response.
- To collect further information on the safety, tolerability, and efficacy of sirolimus in combination with idarubicin/cytarabine in patients with newly diagnosed AML.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822015
|Contact: Margaret Kasner, MD||215-955-8874|
|Contact: Clinical Research Management Office||215-955-1661|
|United States, Pennsylvania|
|Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Margaret Kasner, MD 215-955-8874|
|Contact: Clinical Research Management Office 215-955-1661|
|Principal Investigator: Margaret Kasner, MD|
|Sub-Investigator: Sameh Gaballa, MD|
|Sub-Investigator: Neal Flomenberg, MD|
|Sub-Investigator: Joanne Filicko-O'Hara, MD|
|Sub-Investigator: Mark Weiss, MD|
|Sub-Investigator: S. Onder Alpdogan, MD|
|Sub-Investigator: Ubaldo Martinez-Outschoorn, MD|
|Sub-Investigator: Manish Sharma, MD|
|Sub-Investigator: John Wagner, MD|
|Sub-Investigator: Matthew Carabasi, MD|
|Sub-Investigator: Thomas Klumpp, MD|
|Principal Investigator:||Margaret Kasner, MD||Thomas Jefferson University|