S0919 Idarubicin, Cytarabine, and Pravastatin in Treating Patients With Relapsed Acute Myeloid Leukemia

OBJECTIVES:

- To test whether the complete remission (CR) rate (including CR with incomplete recovery)
in patients with relapsed acute myeloid leukemia treated with idarubicin and cytarabine
in combination with pravastatin is sufficiently high to warrant a phase III
investigation.

- To estimate relapse-free survival and overall survival rates in these patients.

- To estimate the frequency and severity of toxicities of this regimen in these patients.

- To evaluate, in a preliminary manner, whether pre-study cytogenetic features correlate
with response in these patients.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive oral pravastatin once daily on days 1-8, idarubicin
IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Patients
achieving complete remission proceed to consolidation therapy.

- Consolidation therapy: Beginning 30-60 days after the start of induction therapy,
patients receive oral pravastatin once daily on days 1-6 and idarubicin IV over 10-15
minutes and cytarabine IV continuously on days 4 and 5. Treatment repeats approximately
every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

Cohort 1 (MDS transformed to AML) is open to accrual

Cohort 2 (relapsed/refractory AML) is permanently closed to accrual

DISEASE CHARACTERISTICS:

- For patients registered to relapsed/refractory (Cohort 2), morphologically confirmed
diagnosis of acute myeloid leukemia (AML)

- Patient registered to the MDS transformed to AML cohort (Cohort 1) patients must have
a previous morphologically confirmed diagnosis of MDS/CMML. Patients may have received
previous non-intensive therapy (such as: azacitadine, decitabine, low-dose cytarabine,
lenalidomide) given treatment of MDS/CMML (with up to 20% blasts). At time of
registration, patient must have morphologically confirmed diagnosis of AML.

- Patients with acute promyelocytic leukemia (i.e., APL, FAB M3) or blastic
transformation of chronic myelogenous leukemia are not eligible

- Patients mus not have received autologous or allogeneic stem cell transplant.

- Patients in the relapsed/refractory AML cohort (Cohort 2) must:

- Have received ≥ 1 prior chemotherapy regimen for AML

- Any type of prior chemotherapy allowed

- Administration of hydroxyurea to control high WBC prior to, during, and
after registration is permitted

- Relapse must be documented by a bone marrow examination demonstrating > 5% blasts
in the bone marrow not attributable to another cause

- Patient must not have received chemo within 14 days prior to registration

- Primary refractory patients eligible if, on Day 14 of previous chemo regimen, they
have significant residual disease. Patients who received only hypomethylating agent or
low dose therapy for Induction are not considered primary refractory for this study
and are not eligible.

- Relapsed patients must have achieved a complete remission (CR) or CR with incomplete
blood count recovery that lasted < 6 months after the last induction regimen

- No clinical evidence of leptomeningeal disease

- Pretreatment (collected within 28 days of registration) cytogenetics must be performed
on all patients.

- Patients must have complete history and physical exam within 28 days prior to
registration.

PATIENT CHARACTERISTICS:

- No symptomatic congestive heart failure, coronary artery disease, cardiomyopathy, or
uncontrolled arrhythmias

- Ejection fraction ≥ 45% by echocardiogram or MUGA scan within 28 days prior to
registration (or within 14 days prior to registration if the patient has received
anthracycline in the 28 day window)

- Zubrod performance status 0-2

- Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

- Total bilirubin ≤ 2.0 times ULN (unless elevation is primarily due to elevated
unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis AND not
due to liver dysfunction)

- AST and ALT ≤ 3.0 times ULN

- Not pregnant or nursing and negative pregnancy test within 14 days prior to
registration. Females of child-bearing potential must agree to use effective
contraception

- No HIV positivity unless the following criteria are met:

- No history of AIDS-defining events

- CD4 count ≥ 500/mm³

- Viral load < 25,000 copies (< 50 copies if on combination antiretroviral therapy)

- Not receiving zidovudine or stavudine as part of combination antiretroviral
therapy

- No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as
exhibiting ongoing signs/symptoms related to the infection with no improvement despite
appropriate antibiotics or other treatment

- Patients with prior malignancy (other than AML and MDS/CMML) eligible provided patient
is in remission from that malignancy at least 6 months prior to registration. Except
for AML and MDS treatment, all treatment related toxicities must have been resolved.