Everolimus, Cytarabine, and Daunorubicin in Treating Patients With Relapsed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Everolimus may help cytarabine and daunorubicin work better by making cancer cells more sensitive to chemotherapy. Giving everolimus together with cytarabine and daunorubicin may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cytarabine and daunorubicin in treating patients with relapsed acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of everolimus. Determine the toxicity of this regimen. Secondary Assess the activation of PI3K/AKT and mTORC 1 in leukemic blasts. Evaluate the pharmacokinetics of everolimus at different concentrations. OUTLINE: This is a multicenter study. Patients receive primary induction therapy comprising daunorubicin hydrochloride IV on days 1-3, cytarabine IV over 24 hours on day 1, and oral everolimus on days 1 and 7. Patients with more than 5% blasts on day 15 receive a second induction course comprising daunorubicin hydrochloride IV on days 17 and 18 and cytarabine IV twice daily on days 17-20. After completion of study therapy, patients are followed for 3 months.

Official Title
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Phase I Study Evaluating the Chemosensitizing Effect of Everolimus Administered With Cytarabine and Daunorubicin in Patients With Acute Myeloid Leukemia in Relapse

Conditions
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Leukemia

Intervention / Treatment
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* Drug: cytarabine
* Drug: daunorubicin hydrochloride
* Drug: everolimus
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Diagnosis of de novo or secondary acute myeloid leukemia meeting the following criterion: Relapse > 1 year after obtaining complete remission (any prior treatment allowed) Exclusion criteria: Philadelphia chromosome-positive disease in blast crisis FAB M3, M6, or M7 disease PATIENT CHARACTERISTICS: Inclusion criteria: Life expectancy ≥ 4 weeks Transaminases ≤ 5 times normal Creatinine ≤ 2 times normal Bilirubin ≤ 3 times normal (except if visceral involvement present) Alkaline phosphatase or gamma-glutamyltransferase ≤ 5 times normal Not pregnant or nursing Negative pregnancy test Fertile patients of must use effective contraception during and for ≥ 28 days after completion of study therapy Exclusion criteria: FEV1 < 30% Active uncontrolled or viral pulmonary infection Serious psychiatric disorders not related to leukemia or any condition that would prohibit comprehension of the study HIV-positive Other concurrent malignancy except noninvasive skin cancer or carcinoma in situ Patients who are incarcerated or under supervision or trusteeship PRIOR CONCURRENT THERAPY: Inclusion criteria: See Disease Characteristics Exclusion criteria: Prior experimental medication within the past 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cytarabine|nan|
|Drug: daunorubicin hydrochloride|nan|
|Drug: everolimus|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of everolimus |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activation of PI3K/AKT and mTORC 1 in leukemic blasts |  |  | 
| Pharmacokinetics of everolimus |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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)