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

Phase 2

Completed

Conditions: Leukemia

Interventions: Drug: cytarabine
Drug: idarubicin
Drug: pravastatin sodium

Registration Number: NCT00840177

Lead Sponsor: SWOG Cancer Research Network

Brief Summary: RATIONALE: 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 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine together with pravastatin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with pravastatin works in treating patients with relapsed acute myeloid leukemia (AML).

ADDITIONAL BACKGROUND: S0919 was initially designed for patients with relapsed acute myeloid leukemia (AML), where the patient's preceding remission had lasted ≥ 3 months. The null response rate was 30%. The study closed to accrual on Nov 1, 2012 after meeting the defined criterion for a positive study; and the results are being submitted to the American Society of Clinical Oncology meeting. Based on the promising results from this trial, the trial has now been amended to evaluate this therapeutic regimen in poor-risk patients (patients with newly diagnosed acute myeloid leukemia (AML) arising out of myelodysplastic syndrome (MDS), primary refractory acute myeloid leukemia (AML), and relapsed acute myeloid leukemia (AML) with the patient's preceding remission lasting \< 6 months).

Detailed Description: COHORTS:

Cohort 1 (Initial cohort: Relapsed AML with previous remission ≥ 3 months), Cohort 2 (Poor-risk cohort: MDS transformed to AML), Cohort 3 (Poor-risk cohort: Refractory or relapsed AML with previous remission \< 6 months)

OBJECTIVES:

* To test whether the complete remission (CR) rate (including CR with incomplete recovery) in patients with relapsed acute myeloid leukemia (AML) 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 115

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	idarubicin	Induction (1 cycle): pravastatin 1280 mg/d PO D 1-8 idarubicin 12 mg/m2/d IV D 4-6 cytarabine 1.5 g/m2/d continuous IV D 4-7 Consolidation (up to 2 cycles): pravastatin 1280 mg/d PO D 1-6 idarubicin 12 mg/m2/d IV D 4-5 cytarabine 1.5 g/m2/d continuous IV D 4-5
treatment	cytarabine	Induction (1 cycle): pravastatin 1280 mg/d PO D 1-8 idarubicin 12 mg/m2/d IV D 4-6 cytarabine 1.5 g/m2/d continuous IV D 4-7 Consolidation (up to 2 cycles): pravastatin 1280 mg/d PO D 1-6 idarubicin 12 mg/m2/d IV D 4-5 cytarabine 1.5 g/m2/d continuous IV D 4-5
treatment	pravastatin sodium	Induction (1 cycle): pravastatin 1280 mg/d PO D 1-8 idarubicin 12 mg/m2/d IV D 4-6 cytarabine 1.5 g/m2/d continuous IV D 4-7 Consolidation (up to 2 cycles): pravastatin 1280 mg/d PO D 1-6 idarubicin 12 mg/m2/d IV D 4-5 cytarabine 1.5 g/m2/d continuous IV D 4-5

Primary Outcome Measures

Name	Time	Method
Complete Remission (CR) Rate (Including CR With Incomplete Recovery)	Up to 5 years after registration	Participants who achieved morphological complete remission with or without incomplete blood count recovery. Per the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia, morphologic complete remission requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL.

Secondary Outcome Measures

Name	Time	Method
Frequency and Severity of Toxicity as Assessed by NCI CTCAE Version 3.0	Up to 5 years post registration	Number of patients with Grade 3-5 adverse events that were possibly, probably or definitely related to study drug are reported by given type of adverse event

Trial Locations

Locations (185): University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Stanford Cancer Institute
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Palo Alto, California, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
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Aurora, Colorado, United States
Smilow Cancer Hospital Care Center at Saint Francis
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Hartford, Connecticut, United States
Moffitt Cancer Center
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Tampa, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
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Caldwell, Idaho, United States
Kootenai Medical Center
🇺🇸
Coeur d'Alene, Idaho, United States
Walter Knox Memorial Hospital
🇺🇸
Emmett, Idaho, United States
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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States