Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
|ClinicalTrials.gov Identifier: NCT01822015|
Recruitment Status : Active, not recruiting
First Posted : April 1, 2013
Last Update Posted : April 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Sirolimus Drug: Idarubicin Drug: Cytarabine||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia|
|Actual Study Start Date :||March 15, 2013|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||June 2020|
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.
- Change in measurement of mTOR activation paired with mTOR target inhibition [ Time Frame: Baseline to day 4 ]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 ]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 ]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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01822015
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Margaret Kasner, MD||Thomas Jefferson University|