Clinical Trial: Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia

Brief Summary: This pilot clinical trial studies sirolimus, idarubicin, and cytarabine in treating patients with newly diagnosed acute myeloid leukemia. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sirolimus together with idarubicin and cytarabine may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Change in measurement of mTOR activation paired with mTOR target inhibition [ Time Frame: Baseline to day 4 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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.

Original Secondary Outcome: Same as current

Information By: Thomas Jefferson University

Dates:
Date Received: March 25, 2013
Date Started: March 15, 2013
Date Completion: June 2018
Last Updated: May 10, 2017
Last Verified: May 2017