AzTrials
AzTrials

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 3NCT02085408

Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase 3 study testing Daunorubicin, Cytarabine and Clofarabine in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Megakaryoblastic Leukemia (M7), run by ECOG-ACRIN Cancer Research Group at 269 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This randomized phase III trial studies clofarabine to see how well it works compared with daunorubicin hydrochloride and cytarabine when followed by decitabine or observation in treating older patients with newly diagnosed acute myeloid leukemia. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Daunorubicin, Cytarabine and Clofarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
727 participants
Where
269 sitesin 3 countries
Study dates
4 Feb 2011to 21 Dec 2022
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin =< grade 1
  • Newly-diagnosed AML patients according to World Health Organization (WHO) classification who are considered candidates for intensive chemotherapy based upon examination of peripheral blood or bone marrow aspirate specimens or touch preparations of the bone marrow biopsy obtained within two weeks prior to randomization; a bone marrow aspirate is required for enrollment; however, on occasion there is discordance between percentage of myeloblasts on the differential of the peripheral blood or aspirate; the peripheral blood criteria are sufficient for diagnosis; confirmatory immunophenotyping will be performed centrally
  • ECOG performance status (PS) 0-3 (restricted to ECOG PS 0-2 if >= 70 years of age)
  • Patients with secondary AML are eligible for enrollment onto the trial; secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML
  • Total serum bilirubin =< 1.5 times upper limit of normal (ULN) (=< grade 1); if total bilirubin is 2 to 3 mg/dL, but direct bilirubin is normal, then the patient will be considered eligible
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  • Patients with a serum creatinine > 1 are eligible if they have a calculated glomerular filtration rate (GFR) of >= 60 ml/min (i.e. class I or class II chronic kidney disease ) using the Modification of Diet in Renal Disease (MDRD) formula
  • Note: Daily creatinine and MDRD formula are only for the 1st induction cycle
  • Cardiac ejection fraction >= 45% or within institutional normal limits; a nuclear medicine gated blood pool examination is preferred; a two-dimensional (2-D) echocardiogram (ECHO) scan is acceptable if a calculated ejection fraction is obtained and follow-up measurement of the cardiac ejection fraction will also be performed by echocardiography; measurement of cardiac ejection fraction should be within two weeks prior to receiving treatment
  • NOTE: when a multi gated acquisition scan (MUGA) or echocardiogram cannot be obtained due to weekend or holiday, then patients may be enrolled provided there is no history of significant cardiovascular disease and a measurement of cardiac ejection fraction will be performed within 5 days of study enrollment
  • Patients with suspected central nervous system (CNS) involvement should undergo lumbar puncture
  • Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (>10^9/l) from peripheral blood
  • HLA typing should be performed at registration, if possible
  • Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing
  • NOTE: All patients achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) will receive consolidation when fit
  • NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation treatment
  • Consolidation cycle 1 must commence within sixty days of the bone marrow aspirate and biopsy that confirmed the presence of a CR or CRi
  • Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant)
  • Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
  • ECOG performance status of 0-2
  • Patients must have resolved any serious infectious complications related to induction
  • NOTE: Patients with an HLA-matched donor and proceeding to transplant will be allowed up to one cycle of consolidation treatment
  • Any significant medical complications related to induction must have resolved
  • Patients must have a creatinine and AST =< grade 1 within 48 hours prior to registration
  • Maintenance should commence within 60 days of recovery of peripheral blood counts after consolidation cycle 2; patients must begin consolidation cycle 2 within 60 days of recovery to be eligible for further therapy
  • Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy and cytogenetic analysis
  • ECOG performance status of 0 -2
  • Patients must have resolved any serious infectious complications related to consolidation cycle 2
  • Any significant medical complications related to consolidation cycle 2 must have resolved
  • Total serum bilirubin =< 1.5 x ULN
  • NOTE: if total bilirubin is 2-3 mg/dL, but direct bilirubin is normal, then the patient will be considered eligible
  • Serum creatinine =< grade 1
  • The absolute neutrophil count (ANC) must be > 1000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover
  • The platelet count must be > 75,000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover
  • Patients must be > 28 days from the start of induction or re-induction chemotherapy, or from the start Consolidation Cycle 1 (if received) and < 90 days following recovery from most recent treatment; and they must have achieved and maintained a response to induction therapy (CR, CRi, or "morphologic disease-free state")
  • Patients must have recovered from the effects of induction, re-induction, or consolidation chemotherapy (all toxicities =< grade I with the exception of reversible electrolyte abnormalities), and have no ongoing active infection requiring treatment
  • Patients must have a total serum bilirubin =< 1.5 x ULN (grade =< 1) and a serum creatinine =< grade 1; AST <= grade 1
  • An eligible HLA-identical donor (either related or unrelated) should be available; in sibling donors, low resolution HLA typing (A,B,DR) will be considered sufficient; in the case of unrelated donors, high-resolution class I and II typing (A, B, C, DRB1 and DQ) should be matched at all 10 loci; donors must be willing and able to undergo peripheral blood progenitor mobilization
  • HLA-identical sibling (6/6): the donor must be determined to be an HLA-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)
  • Matched unrelated donor (10/10): high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRBL, and -DQB1
  • NOTE: for matched donors - will allow select 1 antigen mismatched sibling donors and unrelated donors in accordance with site institutional standard, as long as matched at HLA-A, HLA-B, HLA-C, and DRB1, and with advanced discussion/approval by the Study Chair and the bone marrow transplant (BMT) co-chair
  • Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance
  • Patients must have a cardiac ejection fraction of >= 40%, or within institutional normal limits; a nuclear medicine gated blood pool examination is preferred; a 2-D ECHO scan is acceptable if a calculated ejection fraction is obtained and follow-up measurement of the cardiac ejection fraction will also be performed by echocardiography; measurement of cardiac ejection fraction should be within two weeks prior to allogeneic transplantation
  • Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease

Who cannot join

  • Concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS])
  • Active, uncontrolled infection
  • Acute promyelocytic leukemia (APL) confirmed either by the presence of t(15;17)(q22;q21) or promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha transcripts
  • Blastic transformation of chronic myelogenous leukemia
  • Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine
  • Prior chemotherapy for AML with the exception of hydroxyurea for increased blast count or leukapheresis for leukocytosis
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  • Documented CNS involvement
  • Previous treatment for antecedent hematological disorders (AHD) with 5-azacitidine, decitabine, or low dose cytarabine
  • Human immunodeficiency virus (HIV) infection
  • Hypersensitivity to Escherichia (E.) coli-derived products
  • Human immunodeficiency virus (HIV) infection; patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies

Trial locations and contacts

269 sites in 3 countries.

269 sites in 3 countries

United States266 sites

  • Kapiolani Medical Center at Pali Momi

    ‘Aiea, Hawaii, 96701

  • Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi

    ‘Aiea, Hawaii, 96701

  • Summa Akron City Hospital

    Akron, Ohio, 44304

  • Akron General Medical Center

    Akron, Ohio, 44307

  • Lehigh Valley Hospital

    Allentown, Pennsylvania, 18105

  • Saint Anthony's Health

    Alton, Illinois, 62002

  • McFarland Clinic

    Ames, Iowa, 50010

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106-0995

  • Michigan Cancer Research Consortium Community Clinical Oncology Program

    Ann Arbor, Michigan, 48106

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Atlanta Regional CCOP

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Saint Joseph's Hospital of Atlanta

    Atlanta, Georgia, 30342

  • Georgia Regents University

    Augusta, Georgia, 30912

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Well Star Cobb Hospital

    Austell, Georgia, 30106

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Summa Barberton Hospital

    Barberton, Ohio, 44203

  • Ochsner Clinic Foundation-Baton Rouge

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Saint Francis Hospital and Health Centers

    Beech Grove, Indiana, 46107

  • Sanford Clinic North-Bemidgi

    Bemidji, Minnesota, 56601

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Mecosta County Medical Center

    Big Rapids, Michigan, 49307

  • Montana Cancer Consortium CCOP

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Hematology-Oncology Centers of the Northern Rockies PC

    Billings, Montana, 59102

  • Billings Clinic

    Billings, Montana, 59107-7000

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61701

  • Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Saint Alphonsus Regional Medical Center

    Boise, Idaho, 83706

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Boulder Community Hospital

    Boulder, Colorado, 80301

  • Bozeman Deaconess Cancer Center

    Bozeman, Montana, 59715

  • Bozeman Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Caritas Saint Elizabeth's Medical Center

    Brighton, Massachusetts, 02135-2997

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Graham Hospital Association

    Canton, Illinois, 61520

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • Rocky Mountain Oncology

    Casper, Wyoming, 82609

  • West Virginia University Charleston

    Charleston, West Virginia, 25304

  • Erlanger Medical Center

    Chattanooga, Tennessee, 37403

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • Hematology and Oncology Associates

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • The Jewish Hospital

    Cincinnati, Ohio, 45236

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Samaritan North Health Center

    Dayton, Ohio, 45415

  • Dayton CCOP

    Dayton, Ohio, 45420

  • Oakwood Hospital

    Dearborn, Michigan, 48124

  • Dekalb Medical Center

    Decatur, Georgia, 30033

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Saint Anthony Central Hospital

    Denver, Colorado, 80204

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Exempla Saint Joseph Hospital

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • Colorado Cancer Research Program CCOP

    Denver, Colorado, 80224-2522

  • Wayne State University

    Detroit, Michigan, 48202

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Essentia Health Duluth Clinic CCOP

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Union Hospital of Cecil County

    Elkton, Maryland, 21921

  • Swedish Medical Center

    Englewood, Colorado, 80110

  • Eureka Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Sanford Clinic North-Fargo

    Fargo, North Dakota, 58122

  • Sanford Medical Center-Fargo

    Fargo, North Dakota, 58122

  • Piedmont Fayette Hospital

    Fayetteville, Georgia, 30214

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Hurley Medical Center

    Flint, Michigan, 48502

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

    Fort Wayne, Indiana, 46845

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • University of Florida

    Gainesville, Florida, 32610

  • Illinois CancerCare Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Genesys Regional Medical Center

    Grand Blanc, Michigan, 48439

  • Grand Rapids Clinical Oncology Program

    Grand Rapids, Michigan, 49503

  • Saint Mary's Health Care

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Benefis Healthcare- Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Saint Francis Hospital and Medical Center

    Hartford, Connecticut, 06105

  • Illinois CancerCare-Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Northern Montana Hospital

    Havre, Montana, 59501

  • Geisinger Medical Center-Cancer Center Hazelton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Park Ridge Hospital Breast Health Center

    Hendersonville, North Carolina, 28792

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Hematology Oncology Associates of Illinois-Highland Park

    Highland Park, Illinois, 60035

  • Hinsdale Hematology Oncology Associates Incorporated

    Hinsdale, Illinois, 60521

  • Oncare Hawaii Inc-POB II

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • OnCare Hawaii-Liliha

    Honolulu, Hawaii, 96817-3169

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Oncare Hawaii Inc-Kuakini

    Honolulu, Hawaii, 96817

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Franciscan St. Francis Health

    Indianapolis, Indiana, 46237

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Jackson-Madison County General Hospital

    Jackson, Tennessee, 38301

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Castle Medical Center

    Kailua, Hawaii, 96734

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Glacier Oncology PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology

    Kalispell, Montana, 59901

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • Presence Saint Mary's Hospital

    Kankakee, Illinois, 60901

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Kinston Medical Specialists PA

    Kinston, North Carolina, 28501

  • Gundersen Lutheran

    La Crosse, Wisconsin, 54601

  • Carolina Blood and Cancer Care Associates PA-Lancaster

    Lancaster, South Carolina, 29720

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Gwinnett Medical Center

    Lawrenceville, Georgia, 30045

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • University of Kentucky

    Lexington, Kentucky, 40536

  • North Shore Hematology Oncology

    Libertyville, Illinois, 60048

  • Wilcox Memorial Hospital and Kauai Medical Clinic

    Lihue, Hawaii, 96766

  • Saint Rita's Medical Center

    Lima, Ohio, 45801

  • Littleton Adventist Hospital

    Littleton, Colorado, 80122

  • Saint Mary Mercy Hospital

    Livonia, Michigan, 48154

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • Norton Health Care Pavilion - Downtown

    Louisville, Kentucky, 40202

  • McKee Medical Center

    Loveland, Colorado, 80539

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Mcdonough District Hospital

    Macomb, Illinois, 61455

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Wellstar Kennestone Hospital

    Marietta, Georgia, 30060

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Providence Milwaukie Hospital

    Milwaukie, Oregon, 97222

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Montana Cancer Specialists

    Missoula, Montana, 59802

  • Saint Patrick Hospital - Community Hospital

    Missoula, Montana, 59802

  • Holy Family Medical Center

    Monmouth, Illinois, 61462

  • Illinois CancerCare-Monmouth

    Monmouth, Illinois, 61462

  • West Virginia University

    Morgantown, West Virginia, 26506

  • D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • Mercy Health Partners-Mercy Campus

    Muskegon, Michigan, 49444

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Ochsner Baptist Medical Center

    New Orleans, Louisiana, 70115

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Illinois Cancer Specialists-Niles

    Niles, Illinois, 60714

  • Bromenn Regional Medical Center

    Normal, Illinois, 61761

  • Community Cancer Center Foundation

    Normal, Illinois, 61761

  • Illinois CancerCare-Community Cancer Center

    Normal, Illinois, 61761

  • Oconomowoc Memorial Hospital-ProHealth Care Inc

    Oconomowoc, Wisconsin, 53066-3896

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Florida Hospital

    Orlando, Florida, 32803

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Ottawa Regional Hospital and Healthcare Center

    Ottawa, Illinois, 61350

  • Parker Adventist Hospital

    Parker, Colorado, 80138

  • Pekin Cancer Treatment Center

    Pekin, Illinois, 61554

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61603

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61603

  • Proctor Hospital

    Peoria, Illinois, 61614

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Illinois Oncology Research Association CCOP

    Peoria, Illinois, 61615

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Illinois Valley Hospital

    Peru, Illinois, 61354

  • Abramson Cancer Center of The University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341-2985

  • Saint Joseph Mercy Port Huron

    Port Huron, Michigan, 48060

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Columbia River Oncology Program

    Portland, Oregon, 97225

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Perry Memorial Hospital

    Princeton, Illinois, 61356

  • Saint Mary Corwin Medical Center

    Pueblo, Colorado, 81004

  • Spectrum Health Reed City Hospital

    Reed City, Michigan, 49677

  • Reid Hospital and Health Care Services

    Richmond, Indiana, 47374

  • Southern Regional Medical Center

    Riverdale, Georgia, 30274

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Carolina Blood and Cancer Care Associates PA

    Rock Hill, South Carolina, 29732

  • Swedish American Hospital

    Rockford, Illinois, 61104

  • Harbin Clinic Medical Oncology and Clinical Research

    Rome, Georgia, 30165

  • Saint Mary's of Michigan

    Saginaw, Michigan, 48601

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Saint Nicholas Hospital

    Sheboygan, Wisconsin, 53081

  • Welch Cancer Center

    Sheridan, Wyoming, 82801

  • Siouxland Hematology Oncology Associates

    Sioux City, Iowa, 51101

  • Mercy Medical Center-Sioux City

    Sioux City, Iowa, 51104

  • Saint Luke's Regional Medical Center

    Sioux City, Iowa, 51104

  • Sanford Cancer Center-Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Medical X-Ray Center

    Sioux Falls, South Dakota, 57105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Hematology Oncology Associates of Illinois - Skokie

    Skokie, Illinois, 60076

  • Providence Hospital

    Southfield, Michigan, 48075

  • Spartanburg Regional Medical Center

    Spartanburg, South Carolina, 29303

  • Upstate Carolina CCOP

    Spartanburg, South Carolina, 29303

  • Illinois CancerCare-Spring Valley

    Spring Valley, Illinois, 61362

  • Memorial Medical Center

    Springfield, Illinois, 62781-0001

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Saint Louis Cancer and Breast Institute-South City

    St Louis, Missouri, 63109

  • Saint Louis University Hospital

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • Saint Louis-Cape Girardeau CCOP

    St Louis, Missouri, 63141

  • Geisinger Medical Group

    State College, Pennsylvania, 16801

  • Mount Nittany Medical Center

    State College, Pennsylvania, 16803

  • North Suburban Medical Center

    Thornton, Colorado, 80229

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Arizona Cancer Center at University Medical Center North

    Tucson, Arizona, 85719

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • PeaceHealth Southwest Medical Center

    Vancouver, Washington, 98664

  • Northwest Cancer Specialists

    Vancouver, Washington, 98684

  • Saint John Macomb-Oakland Hospital

    Warren, Michigan, 48093

  • Waukesha Memorial Hospital - ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Exempla Lutheran Medical Center

    Wheat Ridge, Colorado, 80033

  • Geisinger Wyoming Valley

    Wilkes-Barre, Pennsylvania, 18711

  • Clinton Memorial Hospital

    Wilmington, Ohio, 45177

  • Greene Memorial Hospital

    Xenia, Ohio, 45385

  • York Hospital

    York, Pennsylvania, 17405

Other trials in United States

Israel2 sites

  • Rambam Medical Center

    Haifa, 31096

  • Shaare Zedek Medical Center

    Jerusalem, 91031

Other trials in Israel

India1 site

  • Mayo Clinic Methodist Hospital

    Nagpur, 440 018

Other trials in India

About this study

Official title: Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin &Amp; Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Followed by Decitabine Maintenance vs. Observation in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age >/= 60 Years)

This randomized phase III trial studies clofarabine to see how well it works compared with daunorubicin hydrochloride and cytarabine when followed by decitabine or observation in treating older patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as clofarabine, daunorubicin hydrochloride, cytarabine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective in treating acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the effect of clofarabine induction and consolidation therapy on overall survival in comparison with standard therapy (daunorubicin [daunorubicin hydrochloride] \& cytarabine) in newly-diagnosed acute myeloid leukemia (AML) patients age >= 60 years.

SECONDARY OBJECTIVES:

  1. To evaluate complete remission (CR) rates, duration of remission, and toxicity/treatment-related mortality of clofarabine in comparison with standard therapy (daunorubicin \& cytarabine) in newly-diagnosed AML patients age >= 60 years.

II. To evaluate the feasibility of consolidation with reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical donors in patients who achieve a response to induction therapy, including the incidence of successful engraftment, acute and chronic graft-versus-host disease, transplant-related mortality, and its impact on overall survival in comparison to patients receiving chemotherapy.

III. To evaluate the duration of remission and disease-free survival of patients in complete remission following completion of consolidation therapy who are subsequently randomized to receive scheduled low-dose decitabine maintenance in comparison with observation.

IV. To perform expression and methylation profiling on all patients receiving decitabine and to correlate their integrated epigenetic signatures with response to decitabine.

  1. To examine the epigenetic profiles of remission marrow in patients randomized to observation vs. decitabine to determine whether epigenetic signature of apparently morphologically normal bone marrow is predictive of relapse or response to decitabine maintenance.

VI. To explore the possible association of response to clofarabine with ABC-transporter P-glycoprotein (Pgp).

VII. To assess the intensity of expression of CXC chemokine receptor type 4 (CXCR4) on diagnostic leukemia cells and to correlate this parameter with other established prognostic factors.

VIII. To assess the entire spectrum of somatic mutations and affected pathways at diagnosis of AML and elucidate the association between gene mutation and outcome.

IX. To examine the impact of smoking, obesity, regular acetaminophen use, regular aspirin use, benzene exposure, living in a rural/farm environment and some other underlying exposures and lifestyle factors associated with AML development on overall survival (OS).

  1. To investigate potential correlative results between array comparative genomic hybridization (CGH) findings and acute myeloid leukemia patient characteristics.

TERTIARY OBJECTIVES:

  1. To compare health-related quality of life (QOL) (physical, functional, leukemia-specific well-being) and fatigue in elderly AML patients receiving standard induction therapy with those receiving clofarabine.

II. To measure the change in health-related QOL that occurs over time (within treatment groups).

III. To comprehensively assess patient function at the time of study enrollment.

IV. To determine if components of a comprehensive geriatric assessment or QOL scales predict ability to complete AML treatment.

  1. To describe the impact of transplant on QOL in AML patients above age 60.

OUTLINE:

INDUCTION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM A (STANDARD THERAPY): Patients receive daunorubicin hydrochloride at 60 mg/m^2 intravenously (IV) over 10-15 minutes on days 1-3 and cytarabine at 100 mg/m^2 IV continuously on days 1-7. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., < 5% blasts and < 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 14.

ARM B: Patients receive clofarabine at 30 mg/m^2 IV over 1 hour on days 1-5. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., < 5% blasts and < 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 21 and no later than day 56.

Patients who achieve a complete remission (CR) or CR with incomplete marrow recovery (CRi) after induction therapy proceed to consolidation therapy (Arms C and D). Patients who are 60-69 years of age who achieve a "morphologic leukemia-free state" after induction therapy and who have an HLA-identical donor proceed to allogeneic stem cell transplantation.

CONSOLIDATION THERAPY: Beginning within 60 days after documentation of CR or CRi, patients receive consolidation therapy in the same arm they were randomized to for induction therapy.

ARM C (STANDARD THERAPY): Patients receive cytarabine at 1500 mg/m^2 IV over 1 hour once or twice daily on days 1-6. Treatment repeats every 4-6 weeks for 2 courses.

ARM D: Patients receive clofarabine at 20 mg/m^2 IV over 1 hour on days 1-5. Treatment repeats every 4-6 weeks for 2 courses.

Patients who remain in CR after completion of consolidation therapy are randomized to one of the two maintenance therapy arms (Arms E and F).

MAINTENANCE THERAPY: Beginning within 60 days after completion of consolidation therapy, patients receive maintenance therapy and are randomized to 1 of 2 arms. Patients not eligible for randomization to decitabine maintenance after recovery from consolidation will be followed according to Arm E.

ARM E: Patients undergo observation monthly for 12 months.

ARM F: Patients receive decitabine at 20 mg/m^2 IV over 1 hour on days 1-3. Treatment repeats every 4 weeks for 12 months the absence of unacceptable toxicity.

ALLOGENEIC STEM CELL TRANSPLANTATION WITH REDUCED-INTENSITY CONDITIONING REGIMEN (Arm G): Patients begin reduced-intensity conditioning 30-90 days after the initiation of induction therapy.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate at 30 mg/m^2 IV over 30 minutes on days -7 to -3, busulfan at 0.8 mg/kg IV over 2 hours every 6 hours on days -4 and -3 (for a total of 8 doses), and anti-thymocyte globulin at 2.5 mg/kg/day IV over 4-6 hours on days -4 to -2.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 4 years, every 6 months for 1 year, and then annually thereafter.

Being tested
Daunorubicin, Cytarabine, Clofarabine, Decitabine, Observation
Keywords
acute myeloid leukemia, Clofarabine, Daunorubicin, Cytarabine, Decitabine
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaunorubicinDrug

    Also called Daunomycin, Cerubidine, Rubidomycin

    Given IV

  • CytarabineDrug

    Also called Ara-C, Arabinosyl, Cytosar-U, cytosine arabinoside

    Given IV

  • ClofarabineDrug

    Also called CLOLAR, Cl-F-Ara-A, 2-chloro-9-(2-deoxy-2-fluoro-β-Darabinofuranosyl)adenine

    Given IV

  • DecitabineDrug

    Also called Dacogen®, 5-aza-2'-deoxycytidine, 5-aza-CdR

    Given IV

  • ObservationOther

    Undergo clinical observation

  • Allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Also called AlloSCT

    Patients with an HLA-identical donor proceed to allogeneic stem cell transplantation.

Study groups in NCT02085408
Study groupRoleWhat they receive
A (Induction:daunorubicin/cytarabine; consolidation:cytarabine; maintenance:observation/transplant)Active comparatorSee Detailed Description
Receives: Drug: Daunorubicin; Drug: Cytarabine; Other: Observation; Procedure: Allogeneic hematopoietic stem cell transplantation
B (Induction: clofarabine; Consolidation: clofarabine; Maintenance: decitabine or transplant)ExperimentalSee Detailed Description
Receives: Drug: Clofarabine; Drug: Decitabine; Procedure: Allogeneic hematopoietic stem cell transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Overall survival is defined as the time from randomization to death or date last known alive.

    Measured: Assessed every 3 months for 4 years and then every 6 months for 1 year

Secondary outcomes (3)

  1. Proportion of Patients With Complete Remission

    Patients are required to have all of the following to be considered as having a completion remission (CR).

    • Peripheral Blood Counts
    1. Neutrophil count > 1.0 x 10^9 /L
    2. Platelet count ≥ 100 x 10^9 /L
    3. Reduced hemoglobin concentration or hematocrit has no bearing on remission status
    4. Leukemic blasts must not be present in the peripheral blood
    • Bone Marrow Aspirate and Biopsy
    1. Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines
    2. < 5% blasts by morphologic review
    3. Auer rods must not be detectable
    • Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present

    Measured: Assessed every 3 months for 4 years and then every 6 months for 1 year

  2. Overall Survival by Donor Status

    Overall survival is defined as time between achieving leukemia-free state after induction therapy to death from any cause or date last known alive. The association between overall survival and donor status was evaluated regardless of assigned treatment arms. Patients with transplant donor information (either had donor or did not have a donor) reported after achieving CR/Cri/leukemia-free state post induction therapy were included in this analysis.

    Measured: Assessed every 3 months for 4 years and then every 6 months for 1 year

  3. Disease-free Survival for Maintenance

    DFS for maintenance comparison is defined as the time from maintenance randomization until relapse or death of any cause. The censored follow-up time for patients without relapse and death information is the date of last contact. Only patients who remained in CR or CRi after completion of consolidation therapy that were randomized to either observation or decitabine in the maintenance Step were included in this analysis.

    Measured: Assessed every 3 months for 4 years and then every 6 months for 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2014 (estimated)
  2. Study start4 Feb 2011
  3. Primary completion22 Feb 2021
  4. Study completion21 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
727 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02085408
Sponsor's protocol ID
E2906
Other IDs
NCI-2011-01992, CDR0000659585, E2906, E2906, U10CA021115
Status last verified
Nov 2024
First submitted
11 Mar 2014
Last updated
13 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Publications

  • Foran JM, Sun Z, Luger SM, Claxton DF, Lazarus HM, Arber DA, Rowe JM, Paietta E, Racevskis J, Garrett-Bakelman F, Zhang Y, Altman JK, Al-Kali A, Zheng H, Pratz KW, Broun ER, Powell BL, O'Dwyer KM, Godwin JE, Ofran Y, Litzow MR, Tallman MS. Survival after intensive therapy or clofarabine in fit older adults with acute myeloid leukemia: E2906 phase 3 trial. Blood Neoplasia. 2026 Jan 14;3(2):100194. doi: 10.1016/j.bneo.2026.100194. eCollection 2026 May.

    PubMed 41890705

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