Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Study Overview
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Brief Summary
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This clinical trial studies idarubicin, cytarabine, and pravastatin sodium in treating patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndromes. 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. Pravastatin sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving idarubicin and cytarabine together with pravastatin sodium may kill more cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the rate of achieving a good complete response (CR) after treating patients with newly diagnosed acute myeloid leukemia (AML) with idarubicin, cytarabine and pravastatin (pravastatin sodium) (IAP). II. To determine the toxicity (death within 28 days of starting therapy = treatment related mortality or TRM) with IAP in newly-diagnosed AML. SECONDARY OBJECTIVES: I. To determine rates of complete remission (CR), remission with incomplete blood count recovery (CRi), partial remission (PR), relapse-free survival and overall survival. II. To identify biomarkers (ie. changes in serum cholesterol) associated with clinical responses. OUTLINE: Patients receive pravastatin sodium orally (PO) once daily (QD) on days 1-8, idarubicin intravenously (IV) over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.

Official Title
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Idarubicin, Cytarabine and Pravastatin (IAP) for Induction of Newly Diagnosed Acute Myeloid Leukemia (AML)

Conditions
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Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), 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), Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Refractory Anemia With Excess Blasts, Untreated Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: pravastatin sodium
* Drug: idarubicin
* Drug: cytarabine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of acute myeloid leukemia by World Health Organization (WHO) 2008 criteria, including patients with >= 20% blasts in the bone marrow or peripheral blood (except acute promyelocytic leukemia), or myelodysplastic syndrome refractory anemia with excess blasts (RAEB)-2 by WHO classification or advanced myeloproliferative neoplasm with >= 10% blasts in the bone marrow or peripheral blood, including chronic myelomonocytic leukemia (CMML) CMML-2 by WHO 2008 classification Untreated AML or high-risk myelodysplastic syndrome (MDS) and a simplified TRM score of =< 9.2 Bilirubin < 2.0 mg/ml Any creatinine value is acceptable Any performance status is eligible Life expectancy otherwise > 1 year Patients are not excluded based on cardiac history Females of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment Patients must use an effective contraceptive method during the study and for a minimum of 90 days after study treatment Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Treatment (pravastatin sodium, idarubicin, and cytarabine)<br>Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. | Drug: pravastatin sodium<br>* Given PO<br>* Other names: Pravachol;Drug: idarubicin<br>* Given IV<br>* Other names: IDA;Drug: cytarabine<br>* Given IV<br>* Other names: cytosine arabinoside;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Good Complete Remission (CR) | A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. Definition of Good CR: Conventional criteria for CR (absolute neutrophil count > 1,000/uL, platelet count > 100,000/uL, marrow with <5% morphologic blasts) and additionally the requirements that marrow Minimal Residual Disease (MRD) - detected by 10-color flow cytometry or conventional cytogenetic evaluation - be absent and that the above blood counts be obtained. | 35 days | 
| Number of Participants With TRM. | A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | 1 year after treatment with IAP | 
| Overall Survival | Amount of time a patient lives after treatment with IAP | 1 year after treatment with IAP | 
| Number of Biomarker-positive Participants With Clinical Responses | Biomarkers: FLT3-ITD positive, NPM1 positive, CEBPA. A good CR is defined as <5% blasts in the marrow by morphologic evaluation along with the absence of any MRD by flow cytometry or cytogenetics and recovery of blood counts (platelets >100,00 and absolute neutrophil count >1,000) by day 35 after induction. Cheson AML Response Criteria is used for Morphologic Leukemia Free State, Morphologic Complete Remission, Cytogenetic Complete Remission (CRc), Molecular Complete Remission (CRm), Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR), Treatment Failure, Recurrence (Progressive Disease). | 38 days after dosing | 
| Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR) | Complete remission (CR) - includes patients with good CR and CR with minimal residual disease (MRD); remission with incomplete blood count recovery (CRi), partial remission (PR) | 35 days |