AzTrials
AzTrials

LeukemiaPhase 3NCT00372593

Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase 3 study testing asparaginase, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Children's Oncology Group at 198 sites in 6 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

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Read more about this study

Who is it for?
Ages Up to 29 years
Conditions the study is for
Leukemia
What is being tested?
asparaginase, cytarabine and daunorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,070 participants
Where
198 sitesin 6 countries
Study dates
Aug 2006to 30 Sep 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Up to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute myeloid leukemia (AML)
  • Meets customary criteria for AML with ≥ 20% bone marrow blasts (by WHO classification)
  • Patients with < 20% bone marrow blasts and cytopenia or myelodysplastic syndromes (e.g., chronic myelomonocytic leukemia, refractory anemia (RA), RA with excess blasts, RA with ringed sideroblasts) are eligible provided 1 of the following criteria is met:
  • Karyotypic abnormality characteristic of de novo AML (t[8;21][q22;q22], inv[16][p13q22], t[16;16][p13;q22], or 11q23 abnormalities)
  • Unequivocal presence of megakaryoblasts (by WHO classification)
  • Isolated myeloid sarcoma (i.e., myeloblastoma or chloroma) allowed regardless of bone marrow results
  • Infants < 1 month of age with progressive disease* are eligible NOTE: *Infants < 1 month of age with AML may be given supportive care until it is clear that the leukemia is not regressing (i.e., the disappearance of peripheral blasts and the normalization of peripheral blood counts)
  • Patients with Down syndrome ≥ 4 years of age are eligible
  • No juvenile myelomonocytic leukemia
  • No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
  • No promyelocytic leukemia (M3)
  • No secondary or treatment-related AML
  • Matched family donor criteria (for patients with intermediate-risk or high-risk disease):
  • HLA-A, -B, -C, and beta chain (-DRB1), identical or 1 antigen or allele mismatched by molecular high resolution technique
  • All available first-degree family members (parents and siblings) must be HLA typed
  • No syngeneic donors
  • Matched alternative donor criteria (for patients with high-risk disease):
  • HLA-A, -B, -C, and -DRB1, identical or 1 antigen or allele mismatched donor
  • HLA-A, -B, and -DRB1 4 of 6 antigen matched unrelated cord blood donor
  • Mismatched family member donor with ≥ 1 haplotype match or 5 of 6 antigen phenotypic match

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiation therapy, or any antileukemic therapy
  • Topical or inhalation steroids for other conditions allowed
  • Intrathecal cytarabine given at diagnosis allowed
  • No other prior treatment for AML
  • No concurrent peripheral blood stem cell transplantation in patients with matched family donor

Trial locations and contacts

198 sites in 6 countries.

198 sites in 6 countries

United States178 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308-1062

  • Albany Medical Center Hospital

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87131-5636

  • Tulane Cancer Center Office of Clinical Research

    Alexandria, Louisiana, 71315-3198

  • Texas Tech University Health Sciences Center School of Medicine - Amarillo

    Amarillo, Texas, 79106

  • C.S. Mott Children's Hospital at University of Michigan Medical Center

    Ann Arbor, Michigan, 48109-0286

  • Mission Hospitals - Memorial Campus

    Asheville, North Carolina, 28801

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

    Atlanta, Georgia, 30322

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • MBCCOP - Medical College of Georgia Cancer Center

    Augusta, Georgia, 30912

  • Children's Hospital Center for Cancer and Blood Disorders

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Baltimore, Maryland, 21215

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • CancerCare of Maine at Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Mountain States Tumor Institute at St. Luke's Regional Medical Center

    Boise, Idaho, 83712

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Brooklyn Hospital Center

    Brooklyn, New York, 11201-5493

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Fletcher Allen Health Care - University Health Center Campus

    Burlington, Vermont, 05401

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Health Sciences Center - Charleston

    Charleston, West Virginia, 25302

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Presbyterian Cancer Center at Presbyterian Hospital

    Charlotte, North Carolina, 28233-3549

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • T.C. Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Geisinger Cancer Institute at Geisinger Health

    Danville, Pennsylvania, 17822-0001

  • Children's Medical Center - Dayton

    Dayton, Ohio, 45404

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042-3300

  • CCOP - MeritCare Hospital

    Fargo, North Dakota, 58122

  • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

    Farmington, Connecticut, 06360-2875

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Broward General Medical Center Cancer Center

    Fort Lauderdale, Florida, 33316

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Butterworth Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Leo W. Jenkins Cancer Center at ECU Medical School

    Greenville, North Carolina, 27834

  • Greenville Hospital Cancer Center

    Greenville, South Carolina, 29605

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033-0850

  • Memorial Cancer Institute at Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 96813

  • Baylor University Medical Center - Houston

    Houston, Texas, 77030

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • St. Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207-8426

  • CCOP - Kalamazoo

    Kalamazoo, Michigan, 49008

  • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

    Kansas City, Kansas, 66160-7357

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37916

  • Breslin Cancer Center at Ingham Regional Medical Center

    Lansing, Michigan, 48910

  • CCOP - Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

    Los Angeles, California, 90048-1865

  • Jonsson Comprehensive Cancer Center at UCLA

    Los Angeles, California, 90095-1781

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Children's Hospital Central California

    Madera, California, 93636-8762

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • Cardinal Bernardin Cancer Center at Loyola University Medical Center

    Maywood, Illinois, 60153

  • Banner Desert Medical Center

    Mesa, Arizona, 85202

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Baptist-South Miami Regional Cancer Program

    Miami, Florida, 33176

  • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • University of South Alabama Mitchell Cancer Institute

    Mobile, Alabama, 36604

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • Yale Cancer Center

    New Haven, Connecticut, 06520-8028

  • Schneider Children's Hospital

    New Hyde Park, New York, 11040

  • Children's Hospital of New Orleans

    New Orleans, Louisiana, 70118

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • Keyser Family Cancer Center at Advocate Hope Children's Hospital

    Oak Lawn, Illinois, 60453

  • Children's Hospital and Research Center Oakland

    Oakland, California, 94609

  • Kaiser Permanente Medical Center - Oakland

    Oakland, California, 94611

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital

    Omaha, Nebraska, 68114-4113

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-6805

  • Children's Hospital of Orange County

    Orange, California, 92868-3874

  • Florida Hospital Cancer Institute at Florida Hospital Orlando

    Orlando, Florida, 32803-1273

  • M.D. Anderson Cancer Center at Orlando

    Orlando, Florida, 32806

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Advocate Lutheran General Cancer Care Center

    Park Ridge, Illinois, 60068-1174

  • St. Joseph's Hospital and Medical Center

    Paterson, New Jersey, 07503

  • Sacred Heart Cancer Center at Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134-1095

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Maine Children's Cancer Program at Barbara Bush Children's Hospital

    Portland, Maine, 04102

  • Legacy Emanuel Hospital and Health Center and Children's Hospital

    Portland, Oregon, 97227

  • Knight Cancer Institute at Oregon Health and Science University

    Portland, Oregon, 97239-3098

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708-2197

  • Rhode Island Hospital Comprehensive Cancer Center

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • Carilion Medical Center for Children at Roanoke Community Hospital

    Roanoke, Virginia, 24014

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Sutter Cancer Center

    Sacramento, California, 95816

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229-3900

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123-4282

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Santa Barbara Cottage Children's Hospital

    Santa Barbara, California, 93105

  • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

    Savannah, Georgia, 31403-3089

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Sanford Cancer Center at Sanford USD Medical Center

    Sioux Falls, South Dakota, 57117-5039

  • Providence Cancer Center at Sacred Heart Medical Center

    Spokane, Washington, 99204

  • Simmons Cooper Cancer Institute

    Springfield, Illinois, 62794-9677

  • Baystate Regional Cancer Program at D'Amour Center for Cancer Care

    Springfield, Massachusetts, 01199-0001

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Cancer Center

    Stony Brook, New York, 11794-9446

  • Overlook Hospital

    Summit, New Jersey, 07902

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center - Tacoma

    Tacoma, Washington, 98405

  • Madigan Army Medical Center - Tacoma

    Tacoma, Washington, 98431

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Albert Einstein Cancer Center at Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Toledo Hospital

    Toledo, Ohio, 43606

  • Medical University of Ohio Cancer Center

    Toledo, Ohio, 43614

  • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

    Torrance, California, 90502

  • Tripler Army Medical Center

    Tripler AMC, Hawaii, 96859-5000

  • Arizona Cancer Center at University of Arizona Health Sciences Center

    Tucson, Arizona, 85724-5024

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Walter Reed Army Medical Center

    Washington D.C., District of Columbia, 20307-5001

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

  • UMASS Memorial Cancer Center - University Campus

    Worcester, Massachusetts, 01655

Other trials in United States

Canada11 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 5P9

  • Children's Hospital of Western Ontario

    London, Ontario, N6A 5W9

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

  • Janeway Children's Health and Rehabilitation Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia4 sites

  • Royal Children's Hospital

    Herston, Queensland, 4029

  • Women's and Children's Hospital

    North Adelaide, South Australia, 5006

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

  • Westmead Institute for Cancer Research at Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

New Zealand2 sites

  • Christchurch Hospital

    Christchurch, 8011

  • Starship Children's Health

    Grafton, 1145

Other trials in New Zealand

Switzerland2 sites

  • Swiss Pediatric Oncology Group Bern

    Bern, 3010

  • Swiss Pediatric Oncology Group Geneva

    Geneva, 1205

Other trials in Switzerland

Puerto Rico1 site

  • San Jorge Children's Hospital

    Santurce, 00912

Other trials in Puerto Rico

About this study

Official title: A Phase III Randomized Trial of Gemtuzumab Ozogamicin (Mylotarg) Combined With Conventional Chemotherapy for De Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with gemtuzumab may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab in treating patients with newly diagnosed acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and gemtuzumab to see how well they work compared with combination chemotherapy alone in treating young patients with newly diagnosed acute myeloid leukemia.

Read the detailed description

OBJECTIVES:

Primary

  • Compare the event-free survival (EFS) and overall survival (OS) of young patients with newly diagnosed acute myeloid leukemia (AML) treated with conventional combination chemotherapy with vs without gemtuzumab ozogamicin (GMTZ).

Secondary

  • Compare the remission induction rates after two courses of therapy in these patients.
  • Compare disease-free survival and OS in patients who are eligible for an human leukocyte antigen (HLA)-matched family donor (MFD) stem cell transplant (SCT) by virtue of their risk classification, with patients assigned to MFD SCT if a MFD is available, or to chemotherapy if a MFD is not available.
  • Determine the outcome of patients with Down syndrome who are 4 years of age or older at diagnosis and treated with conventional combination chemotherapy without GMTZ.
  • Compare the EFS and OS of patients with de novo AML treated with conventional combination chemotherapy with vs without GMTZ censoring MFD SCT recipients.
  • Determine the prevalence and prognostic significance of molecular abnormalities of KIT, CCAAT-enhancer binding protein alpha (CEBPα) and MLL-Partial tandem duplications (PTD) genes in these patients.
  • Determine the leukemic involvement of hematopoietic early progenitor and its role in defining response to therapy.
  • Assess the ability of a second-generation flow cytometric assay to predict patients at high risk for relapse during periods of clinical remission.
  • Examine whether GMTZ significantly improves EFS and OS in patients with higher CD33 concentrations/intensity.
  • Examine whether GMTZ significantly improves complete remission, EFS, and OS in each of the cytogenetic risk groups (high-, intermediate-, and low-risk) identified in prior Medical Research Council trials.
  • Utilize fluorescence in situ hybridization (FISH) analysis to identify variant patterns among subgroups of patients who demonstrate the same G-banded chromosomal abnormality (e.g., inv[16]/t[16;16], t[8;21], 11q23 abnormality) and determine whether these variant patterns account for the heterogeneity of responses to therapy.
  • Examine the impact of complex karyotypes (≥ 3, ≥ 4, and ≥ 5 abnormalities) on OS and EFS in intermediate-risk patients for whom no high-risk or low-risk cytogenetic abnormalities exist.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to relapse risk (high vs intermediate vs low). Patients are randomized to 1 of 2 treatment arms. Patients with Down syndrome are nonrandomly assigned to arm I (but do not undergo allogeneic stem cell transplant [SCT]).

  • Arm I (standard therapy):
  • Induction 1: Patients receive cytarabine IT at the time of diagnosis or on day 1*. Patients also receive cytarabine IV on days 1-10, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, all patients (regardless of remission status) proceed to induction 2.

NOTE: *Patients with Central Nervous System (CNS) disease receive cytarabine IT twice weekly until the cerebrospinal fluid is clear, followed by two additional IT treatments. Patients with refractory CNS leukemia after 6 doses of IT treatment are removed from the study.

  • Induction 2: Patients receive cytarabine IT on day 1, cytarabine IV on days 1-8, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, patients in complete remission (CR) proceed to intensification 1. Patients with refractory disease are removed from protocol therapy.
  • Intensification 1: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 1 hour on days 1-5, and etoposide IV over 1 hour on days 1-5. After 3 weeks of rest, patients in remission proceed to intensification 2, followed by intensification 3. Patients in remission proceed to allogeneic SCT 2-8 weeks after blood counts recover. Patients with high-risk disease with an alternative donor proceed to intensification 2 and 3, followed by allogeneic SCT. Patients not in remission are removed from protocol therapy.
  • Intensification 2: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 2 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour on days 3-6. After 3 weeks of rest, patients proceed to intensification 3.
  • Intensification 3: Patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.
  • Arm II:
  • Induction 1: Patients receive treatment as in induction 1 of arm I. Patients also receive gemtuzumab ozogamicin (GMTZ) IV over 2 hours on day 6.
  • Induction 2: Patients receive treatment as in induction 2 of arm I.
  • Intensification 1: Patients receive treatment as in intensification 1 of arm I.
  • Intensification 2: Patients receive treatment as in intensification 2 of arm I. Patients also receive GMTZ IV over 2 hours on day 7.
  • Intensification 3: Patients receive treatment as in intensification 3 of arm I.
  • Allogeneic SCT (for patients with intermediate- or high-risk disease):
  • MFD: Patients receive a conditioning regimen comprising busulfan IV over 2 hours every 6 hours on days -9 to -6 and cyclophosphamide IV over 1 hour on days -5 to -2. Patients undergo allogeneic SCT on day 0. Patients receive cyclosporine IV or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11. Patients receive graft-vs-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1-4 hours or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11.
  • Matched alternative donor: Patients receive a conditioning regimen comprising busulfan and cyclophosphamide as above. Patients also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1. Patients then undergo allogeneic SCT and receive GVHD prophylaxis as above.

After completion of study treatment, patients are followed periodically for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,012 patients will be accrued for this study.

Conditions
Leukemia
Being tested
asparaginase, cytarabine, daunorubicin hydrochloride, etoposide, gemtuzumab ozogamicin
Keywords
adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), untreated adult acute myeloid leukemia, untreated childhood acute myeloid leukemia and other myeloid malignancies, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), childhood acute basophilic leukemia, childhood acute eosinophilic leukemia, childhood acute minimally differentiated myeloid leukemia (M0)
Medical subject headings
Leukemia, Congenital Abnormalities, Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Monocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

  • asparaginaseDrug

    Also called E.coli, E.coli L-asparaginase, EC 3.5.2.2, colaspase

    Given intramuscularly

  • cytarabineDrug

    Also called Cytosine arabinoside, Ara-C, Cytosar, NSC # 63878

    Given IV

  • daunorubicin hydrochlorideDrug

    Also called Daunomycin, rubidomycin, Cerubidine, NSC #82151

    Given IV over 6 hours

  • etoposideDrug

    Also called VePesid, Etopophos, VP-16, NSC #141540

    Given IV over 1-4 hours

  • gemtuzumab ozogamicinDrug

    Also called Mylotarg, GMTZ

    Given IV over 2 hours

  • mitoxantrone hydrochlorideDrug

    Also called Novantrone, CL 232315, DAD, DHAD

    Given IV over 1 hour

Study groups in NCT00372593
Study groupRoleWhat they receive
Arm A: Standard Arm - No GMTZ, AML Pts w/out Down SyndromeActive comparatorPatients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Receives: Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: mitoxantrone hydrochloride
Arm B: Experimental - with GMTZ, AML Pts w/out Down SyndromeExperimentalPts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Receives: Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: gemtuzumab ozogamicin; Drug: mitoxantrone hydrochloride
Arm A: Standard Arm - No GMTZ, AML Patients with Down SyndromeActive comparatorPatients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
Receives: Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: mitoxantrone hydrochloride

What is being measured

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

  1. Event-free Survival at 3 Years

    The Kaplan-Meier method will be used to calculate estimates of Event Free Survival (EFS). The log-rank test will be used to compare survival between treatment groups. Analysis of EFS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to Overall Survival (OS) and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt^2 (truncated at 3 standard deviations) and 2.5% type I error.

    Measured: Time from study entry to time of induction failure, relapse, or death, assessed at 3 years

  2. Overall Survival at 3 Years

    The Kaplan-Meier method will be used to calculate estimates of OS. Analysis of OS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to OS and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt^2 (truncated at 3 standard deviations) and 2.5% type I error.

    Measured: Time from study entry, assessed at 3 years

Secondary outcomes (5)

  1. Remission Induction Rate After 2 Courses of Induction Therapy

    Patients without an evaluable bone marrow at the end of Induction I will be excluded from the calculation of remission rate after 2 courses of therapy because their responses are not evaluable. The following patients will be considered to not be in complete remission (CR) after 2 courses of therapy: (1) patients who die during Induction I and II; (2) patients with ≥ 5% blasts or extramedullary disease at the end of Induction II.

    Measured: After 2 courses of induction (I and II) therapy, assessed for up to 10 years

  2. Disease-free Survival (DFS)

    Time from end of Intensification I to relapse, death or last contact

    Measured: At 3 years from end of Intensification I

  3. Mortality

    Number of participants who died during the first three courses of therapy.

    Measured: During the first three courses of therapy

  4. Time to Marrow Recovery

    Mean time to ANC recovery - defined as ANC greater than 500/MicroLiter for 3 consecutive days.

    Measured: At 25 days after treatment with Induction I, Induction II, and Intensification I

  5. Toxicities, Including Infectious Complications

    Number of participants with at least one grade 3 or higher adverse event during therapy.

    Measured: From the time therapy is initiated, assessed up to 10 years

Timeline

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

  1. First posted7 Sep 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionAug 2013
  4. Study completion30 Sep 2020

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
1,070 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00372593
Sponsor's protocol ID
AAML0531
Other IDs
COG-AAML0531, CDR0000487497, NCI-2009-00320
Status last verified
Feb 2017
First submitted
6 Sep 2006
Last updated
24 Mar 2021
Data monitoring committee
Yes

Publications

  • Pollard JA, Alonzo TA, Loken M, Gerbing RB, Ho PA, Bernstein ID, Raimondi SC, Hirsch B, Franklin J, Walter RB, Gamis A, Meshinchi S. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood. 2012 Apr 19;119(16):3705-11. doi: 10.1182/blood-2011-12-398370. Epub 2012 Feb 29.

    PubMed 22378848

  • Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. doi: 10.1200/JCO.2014.55.3628.

    PubMed 25092781

  • Scheidegger N, Schneider C, Alexe G, Wang YC, Alonzo TA, Basanthakumar A, Bourgeois WA, Dudkiewicz-Garbicz J, Khalid D, Merickel LA, Perry JA, Ries RE, Salhotra S, Taillon A, Gamis A, Aplenc R, Harris MH, Wunderlich M, Armstrong SA, Pollard JA, Meshinchi S, Pikman Y, Stegmaier K. Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia. Blood Adv. 2026 Jul 14;10(13):4757-4771. doi: 10.1182/bloodadvances.2025016208.

    PubMed 42085603

  • Huang BJ, Meyer LK, Alonzo TA, Wang YC, Lamble AJ, Ries RE, Wang W, Hirsch B, Raca G, Ma X, Gamis AS, Aplenc R, Kolb EA, Cooper TM, Tarlock K, Loken MR, Meshinchi S, Chewning JH, Woods WG, Horan JT. Hematopoietic Stem Cell Transplantation Outcomes for High-Risk AML: A Report From the Children's Oncology Group. J Clin Oncol. 2025 Jun 10;43(17):1961-1971. doi: 10.1200/JCO-24-01841. Epub 2025 Apr 28.

    PubMed 40294366

  • Tarlock K, Gerbing RB, Ries RE, Smith JL, Leonti A, Huang BJ, Kirkey D, Robinson L, Peplinski JH, Lange B, Cooper TM, Gamis AS, Kolb EA, Aplenc R, Pollard JA, Alonzo TA, Meshinchi S. Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia. Blood Adv. 2024 May 14;8(9):2094-2103. doi: 10.1182/bloodadvances.2023011980.

    PubMed 38295280

  • Zarnegar-Lumley S, Alonzo TA, Gerbing RB, Othus M, Sun Z, Ries RE, Wang J, Leonti A, Kutny MA, Ostronoff F, Radich JP, Appelbaum FR, Pogosova-Agadjanyan EL, O'Dwyer K, Tallman MS, Litzow M, Atallah E, Cooper TM, Aplenc RA, Abdel-Wahab O, Gamis AS, Luger S, Erba H, Levine R, Kolb EA, Stirewalt DL, Meshinchi S, Tarlock K. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023 Oct 10;7(19):5941-5953. doi: 10.1182/bloodadvances.2022008282.

    PubMed 37267439

  • Bertrums EJM, Smith JL, Harmon L, Ries RE, Wang YJ, Alonzo TA, Menssen AJ, Chisholm KM, Leonti AR, Tarlock K, Ostronoff F, Pogosova-Agadjanyan EL, Kaspers GJL, Hasle H, Dworzak M, Walter C, Muhlegger N, Morerio C, Pardo L, Hirsch B, Raimondi S, Cooper TM, Aplenc R, Gamis AS, Kolb EA, Farrar JE, Stirewalt D, Ma X, Shaw TI, Furlan SN, Brodersen LE, Loken MR, Van den Heuvel-Eibrink MM, Zwaan CM, Triche TJ, Goemans BF, Meshinchi S. Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haematologica. 2023 Aug 1;108(8):2044-2058. doi: 10.3324/haematol.2022.281653.

    PubMed 36815378

  • Elgarten CW, Wood AC, Li Y, Alonzo TA, Brodersen LE, Gerbing RB, Getz KD, Huang YV, Loken M, Meshinchi S, Pollard JA, Sung L, Woods WG, Kolb EA, Gamis AS, Aplenc R. Outcomes of intensification of induction chemotherapy for children with high-risk acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2021 Dec;68(12):e29281. doi: 10.1002/pbc.29281. Epub 2021 Oct 1.

    PubMed 34596937

  • Brodersen LE, Gerbing RB, Pardo ML, Alonzo TA, Paine D, Fritschle W, Hsu FC, Pollard JA, Aplenc R, Kahwash SB, Hirsch B, Ramondi S, Wells D, Kolb EA, Gamis AS, Meshinchi S, Loken MR. Morphologic remission status is limited compared to DeltaN flow cytometry: a Children's Oncology Group AAML0531 report. Blood Adv. 2020 Oct 27;4(20):5050-5061. doi: 10.1182/bloodadvances.2020002070.

    PubMed 33080007

  • Voigt AP, Brodersen LE, Alonzo TA, Gerbing RB, Menssen AJ, Wilson ER, Kahwash S, Raimondi SC, Hirsch BA, Gamis AS, Meshinchi S, Wells DA, Loken MR. Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children's Oncology Group protocol AAML0531. Haematologica. 2017 Dec;102(12):2058-2068. doi: 10.3324/haematol.2017.169029. Epub 2017 Sep 7.

    PubMed 28883080

  • Eidenschink Brodersen L, Alonzo TA, Menssen AJ, Gerbing RB, Pardo L, Voigt AP, Kahwash SB, Hirsch B, Raimondi S, Gamis AS, Meshinchi S, Loken MR. A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children's Oncology Group. Leukemia. 2016 Oct;30(10):2077-2080. doi: 10.1038/leu.2016.119. Epub 2016 May 2. No abstract available.

    PubMed 27133823

  • Sung L, Aplenc R, Alonzo TA, Gerbing RB, Lehrnbecher T, Gamis AS. Effectiveness of supportive care measures to reduce infections in pediatric AML: a report from the Children's Oncology Group. Blood. 2013 May 2;121(18):3573-7. doi: 10.1182/blood-2013-01-476614. Epub 2013 Mar 7.

    PubMed 23471307

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing asparaginase, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Children's Oncology Group at 198 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 198 sites in United States, Canada, Australia, New Zealand, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival at 3 Years (time frame: Time from study entry to time of induction failure, relapse, or death, assessed at 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00372593, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.

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