Sirolimus in Combination With MEC in High Risk Myeloid Leukemias

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the side effects of sirolimus (rapamycin) given in combination with chemotherapy (Mitoxantrone + Etoposide + Cytarabine (MEC)) on high risk myeloid leukemias.

Official Title
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A Prospective Single Institution Pilot Study Evaluating the Pharmacokinetics of Sirolimus in Combination With MEC (Mitoxantrone + Etoposide + Cytarabine) in Patients With High Risk Leukemias

Conditions
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Myeloid Leukemias, AML, Leukemia, CML

Intervention / Treatment
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* Drug: Rapamycin, Mitoxantrone, Etoposide, Cytarabine
* Drug: Rapamycin + MEC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have histologic evidence of advanced myeloid leukemias defined as one of the following: primary refractory non-M3 AML; relapsed non-M3 AML; secondary AML; intermediate or poor prognosis de novo AML in patients who are >= 60 years old >= 18 years of age ECOG performance status of 0, 1 Able to consume oral medication Initial laboratory values: creatinine <= 2.0 mg/dL; total or direct bilirubin <= 1.5/dL; SGPT(ALT) <= 3xULN; negative pregnancy test for women with child-bearing potential Ejection fraction of >= 45% Exclusion Criteria: Subjects with FAM B3 Must not be receiving chemotherapy (except Hydroxyurea) Not receiving growth factors, except for erythropoietin Subjects with a currently active second malignancy other than non-melanoma skin cancers Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, MI within the last 6 months or uncontrolled cardiac arrhythmia Subjects taking diltiazem Subjects who require HIV protease inhibitors or those with AIDS-related illnesses No evidence of cerebellar dysfunction at baseline or during prior cytarabine therapy Not pregnant or breastfeeding Uncontrolled infection Subjects taking Carbamazepine, Rifabutin, Rifampin, Rifapentine, St. John's wort, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Telithromycin, Verapamil, Tacrolimus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin + MEC<br> | Drug: Rapamycin, Mitoxantrone, Etoposide, Cytarabine<br>* Rapamycin loading dose of 12 mg followed by a single daily dose for 8 days of 4 mg/day + MEC (Mitoxantrone 8 mg/m2/day IV, Etoposide 100 mg/m2/day IV and Cytarabine 1000 mg/m2 IV every 24 hours for 5 days. Starts after 4th dose of sirolimus.<br>Drug: Rapamycin + MEC<br>* Rapamycin loading dose of 12 mg followed by a single daily dose for 8 days of 4 mg/day + MEC (Mitoxantrone 8 mg/m2/day IV, Etoposide 100 mg/m2/day IV and Cytarabine 1000 mg/m2 IV every 24 hours for 5 days. Starts after 4th dose of sirolimus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells |  | Study conclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the sirolimus + MEC regimen |  | Study conclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Advanced myeloid leukemias, Leukemia, Relapsed myeloid leukemias, Refractory myeloid leukemias, MEC, Rapamycin, Sirolimus