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

S0919, A Phase II Study of Idarubicin and Ara-C in Combination With Pravastatin for Poor-Risk Acute Myelogenous Leukemia

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).

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: cytarabine; Drug: idarubicin; Drug: pravastatin sodium

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.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Medical Center
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Alphonsus Medical Center-Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Cancer Center
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer Clinic
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Center of Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Radiation Oncology of Northern Illinois
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
    • Swansea, Illinois, United States, 62226
      • Cancer Care Specialists of Illinois-Swansea
    • Swansea, Illinois, United States, 62226
      • Memorial and Saint Elizabeth's Health Care Services LLP
  • Kansas
    • Anthony, Kansas, United States, 67003
      • Hospital District Sixth of Harper County
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Manhattan, Kansas, United States, 66502
      • Cancer Center of Kansas-Manhattan
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Hematology/Oncology Clinic LLP
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center Shreveport
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • IHA Hematology Oncology Consultants-Brighton
    • Canton, Michigan, United States, 48188
      • IHA Hematology Oncology Consultants-Canton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton Health Center
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • IHA Hematology Oncology Consultants-Chelsea
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • East China Township, Michigan, United States, 48054
      • Great Lakes Cancer Management Specialists-Doctors Park
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Michigan Breast Specialists-Grosse Pointe Woods
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Lymphoma Clinic of Michigan
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Livonia, Michigan, United States, 48154
      • Hope Cancer Clinic
    • Macomb, Michigan, United States, 48044
      • Michigan Breast Specialists-Macomb Township
    • Macomb, Michigan, United States, 48044
      • Hematology Oncology Associates East PC
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • 21st Century Oncology-Pontiac
    • Pontiac, Michigan, United States, 48341
      • Hope Cancer Center
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Rochester Hills, Michigan, United States, 48309
      • Great Lakes Cancer Management Specialists-Rochester Hills
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Sterling Heights, Michigan, United States, 48312
      • Bhadresh Nayak MD PC-Sterling Heights
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • Warren, Michigan, United States, 48093
      • Great Lakes Cancer Management Specialists-Macomb Professional Building
    • Warren, Michigan, United States, 48093
      • Macomb Hematology Oncology PC
    • Warren, Michigan, United States, 48093
      • Michigan Breast Specialists-Warren
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
    • Ypsilanti, Michigan, United States, 48197
      • IHA Hematology Oncology Consultants-Ann Arbor
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Medical Center-Goldschmidt Cancer Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • Missouri Baptist Outpatient Center-Sunset Hills
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Billings, Montana, United States, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Wilson, North Carolina, United States, 27893
      • Southeastern Medical Oncology Center-Wilson
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Clinical Oncology Research (SCOR) Consortium NCORP
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Medical Center-Baker City
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • Michael E DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Baylor Saint Luke's Medical Center
  • Washington
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Edmonds, Washington, United States, 98026
      • Swedish Medical Center-Edmonds
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kirkland, Washington, United States, 98034
      • Seattle Cancer Care Alliance at EvergreenHealth
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Sedro-Woolley, Washington, United States, 98284
      • United General Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Cody, Wyoming, United States, 82414
      • Big Horn Basin Cancer Center
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Cohort 1 (Initial cohort: Relapsed AML with previous remission >/= 3 months) is permanently closed to accrual DISEASE CHARACTERISTICS

• Patients must have a previous morphologically confirmed diagnosis of acute myeloid leukemia (AML). Note: This protocol uses the World Health Organization (WHO) diagnostic criteria for acute myeloid leukemia (AML) (see Section 4.1). Patients with acute promyelocytic leukemia (APL, FAB, M3) or blastic transformation of chronic myelogenous leukemia (CMML) are not eligible.
• Patients must have received at least one prior chemotherapy regimen for their acute myeloid leukemia (AML) and they may have received any type of chemotherapy. They must have achieved complete remission (CR), lasting at least three months with their last induction regimen and they must have relapsed after the last regimen. Relapse must be documented by a bone marrow examination demonstrating > 5% blasts in the bone marrow not attributable to another cause. Refractory patients and patients who have received autologous or allogeneic stem cell transplantation are not eligible. Administration of hydroxyurea to control high white blood cell (WBC) count prior to, during and after registration is permitted.
• Patients must not have symptomatic congestive heart failure, coronary artery disease, cardiomyopathy, or uncontrolled arrhythmias. Either an echocardiogram or multiple-gated acquisition (MUGA) scan with an ejection fraction ≥ 45% must be obtained within 28 days prior to registration. (Either method for measuring cardiac function is acceptable, however, the same scan must be used throughout treatment and follow-up to monitor the patient for cardiac toxicity.) If patient has symptoms suggestive of ischemia or congestive heart failure after that cardiac evaluation was done, a repeat study must be obtained prior to registration.
• Patients must have a serum creatinine < 2.0 mg/dl within 14 days prior to registration.
• Patients must have a total bilirubin ≤ 2.0 x Institutional Upper Limit of Normal (IULN) within 14 days prior to registration, unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction.
• Patients must have SGOT (AST) ≤ 3.0 x IULN and SGPT (ALT) ≤ 3.0 x IULN within 14 days prior to registration. Treatment may begin with SGOT/SGPT above those limits, if the abnormalities are thought to be due to the patient's leukemia.
• Patients must have Zubrod performance status of 0-2 (see Section 10.8).
• Patients must be ≥ 18 years of age.
• Patients must not have clinical evidence of leptomeningeal disease (a spinal tap does not need to be performed).

• Patients not known to be HIV+ must be tested for HIV infection (the human immunodeficiency virus) within 14 days prior to registration (see Section 2.0 for justification). Patients who are HIV+ may be eligible providing they meet all of the following additional criteria within 14 days prior to registration:

  1. Patient must have no history of AIDS defining events.
  2. CD4 cells ≥ 500/mm3.
  3. Viral load of < 50 copies HIV mRNA/mm3 if on cART or < 25,000 copies HIV mRNA if not on cART.
  4. No zidovudine or stavudine as part of cART. Patients who are HIV+ and do not meet all of these criteria will not be eligible for this study.
• Patients with prior malignancy (other than AML) are eligible. However, the patient must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy at least 6 months prior to registration and all treatment related toxicities must have been resolved. NOTE: For patients with prior history of malignancy who have received anthracyclines or mediastinal/pericardial radiation in the past, the risk versus benefit of therapy should be weighed, particularly in the setting of receiving consolidation therapy.
• Patients must not have a systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Southwest Oncology Group patients must be registered on SWOG-9007 ("Cytogenetic Studies in Leukemia Patients"). Collection of pretreatment marrow specimens must be completed within 28 days prior to registration. Pretreatment specimens of bone marrow (or peripheral blood if the marrow aspirate is a dry tap) must be submitted to an approved Southwest Oncology Group Cytogenetics Laboratory for cytogenetics analysis. Note that protocol SWOG-9007 also requires submission of specimens at additional timepoints.
• Southwest Oncology Group patients must be offered participation in S9910 ("Leukemia Centralized Reference Laboratories and Tissue Repositories Ancillary"). If consent is given, collection of pretreatment blood and/or marrow specimens must be completed within 28 days prior to registration. If the patient consents to participate in S9910, pretreatment specimens of marrow and/or peripheral blood must be submitted to the Southwest Oncology Group Myeloid Repository at the University of New Mexico for cellular and molecular studies. Note that protocol S9910 also requests submission of specimens at additional timepoints.
• Women of reproductive potential must have a negative pregnancy test within 14 days prior to registration. Patients must not be pregnant or nursing because of the teratogenic potential of the drugs used in this study. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
• At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base.

Cohort 2 (MDS transformed to AML) is permanently closed to accrual AND Cohort 3 (relapsed/refractory AML) is permanently closed to accrual

DISEASE CHARACTERISTICS:

• For patients registered to relapsed/refractory (Cohort 3), morphologically confirmed diagnosis of acute myeloid leukemia (AML)
• Patient registered to the myelodysplastic syndrome (MDS) transformed to acute myeloid leukemia (AML) cohort (Cohort 2) patients must have a previous morphologically confirmed diagnosis of myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML). Patients may have received previous non-intensive therapy (such as: azacitidine, decitabine, low-dose cytarabine, lenalidomide) given treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML) (with up to 20% blasts). At time of registration, patient must have morphologically confirmed diagnosis of acute myeloid leukemia (AML).
• Patients with acute promyelocytic leukemia (i.e., APL, FAB M3) or blastic transformation of chronic myelogenous leukemia are not eligible
• Patients must not have received autologous or allogeneic stem cell transplant.

• Patients in the relapsed/refractory acute myeloid leukemia (AML) cohort (Cohort 3) must:

  • Have received ≥ 1 prior chemotherapy regimen for acute myeloid leukemia (AML)

    • Any type of prior chemotherapy allowed
    • Administration of hydroxyurea to control high white blood cell (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 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treatment, all treatment related toxicities must have been resolved.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment; 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	Drug: cytarabine; 1.5 g/m2/day given by continuous IV on days 4-7; Drug: idarubicin; 12 mg/m2/day given intravenously over 10-15 minutes on days 4-6; Drug: pravastatin sodium; 1,280 mg/day given orally on days 1-8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission (CR) Rate (Including CR With Incomplete Recovery)	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.	Up to 5 years after registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Severity of Toxicity as Assessed by NCI CTCAE Version 3.0	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	Up to 5 years post registration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Pre-study Cytogenetic Features and Response		5 years
Overall Survival (OS)	OS is calculated for all participants from the date of initial registration on study until death from any cause. Observations for participants last known to be alive were censored.	OS assessed for up to 5 years, median OS reported
Relapse-free Survival (RFS)	RFS is calculated for participants who have achieved a complete response (CR) or CR with incomplete blood count recovery (CRi). RFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse. 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.	RFS assessed for up to 5 years, median RFS reported

Collaborators and Investigators

• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Statler A, Othus M, Erba HP, Chauncey TR, Radich JP, Coutre S, Advani A, Nand S, Ravandi F, Mukherjee S, Sekeres MA. Comparable outcomes of patients eligible vs ineligible for SWOG leukemia studies. Blood. 2018 Jun 21;131(25):2782-2788. doi: 10.1182/blood-2018-01-826693. Epub 2018 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2009
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): October 21, 2021

Study Registration Dates

• First Submitted: February 7, 2009
• First Submitted That Met QC Criteria: February 7, 2009
• First Posted (Estimate): February 10, 2009

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); recurrent adult acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Idarubicin; Pravastatin
• Other Study ID Numbers: S0919 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract); NCI-2009-01183 (Other Identifier: NCI)