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

Fred Hutchinson Cancer Center (FHCC)

Status: Completed

Conditions: Adult Acute Megakaryoblastic Leukemia (M7); Adult Erythroleukemia (M6a); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Pure Erythroid Leukemia (M6b); Adult Acute Monoblastic Leukemia (M5a); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Refractory Anemia With Excess Blasts; Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Chronic Myelomonocytic Leukemia; Adult Acute Myeloid Leukemia With Del(5q)

Treatments: Drug: pravastatin sodium; Drug: idarubicin; Other: laboratory biomarker analysis; Drug: cytarabine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01831232

2674.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

NCI-2013-00743 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Treatment (pravastatin sodium, idarubicin, and cytarabine)

Experimental group

Description:

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.

Treatment:

Drug: cytarabine

Other: laboratory biomarker analysis

Drug: idarubicin

Drug: pravastatin sodium