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

NCT00372593 | Completed Phase 3 Results DMC

• 4 other identifiers: AAML0531COG-AAML0531CDR0000487497NCI-2009-00320
• Study Type: interventional
• Target: 1,070
• Locations: 6 countries
• Sites: 198

Brief 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. 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.

Conditions

Leukemia

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); childhood acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia with maturation (M2); childhood acute myelomonocytic leukemia (M4); childhood acute monocytic leukemia (M5b); childhood acute monoblastic leukemia (M5a); childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7)

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  Time from study entry, assessed at 3 years

Secondary Outcomes (5)

• Remission Induction Rate After 2 Courses of Induction Therapy

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

• Disease-free Survival (DFS)

  At 3 years from end of Intensification I

• Mortality

  During the first three courses of therapy

• Time to Marrow Recovery

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

• Toxicities, Including Infectious Complications

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

Study Arms (3)

Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome

ACTIVE COMPARATOR

Patients 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.

Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: mitoxantrone hydrochloride

Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

EXPERIMENTAL

Pts 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.

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 Syndrome

ACTIVE COMPARATOR

Patients 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.

Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: mitoxantrone hydrochloride

Interventions

asparaginase DRUG

Given intramuscularly

Also known as: E.coli, E.coli L-asparaginase, EC 3.5.2.2, colaspase, L-asnase, Elspar, Kidrolase, Crasnitin, Leunase, NSC 109229

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome; Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome; Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

cytarabine DRUG

Given IV

Also known as: Cytosine arabinoside, Ara-C, Cytosar, NSC # 63878

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome; Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome; Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

daunorubicin hydrochloride DRUG

Given IV over 6 hours

Also known as: Daunomycin, rubidomycin, Cerubidine, NSC #82151

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome; Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome; Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

etoposide DRUG

Given IV over 1-4 hours

Also known as: VePesid, Etopophos, VP-16, NSC #141540

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome; Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome; Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

gemtuzumab ozogamicin DRUG

Given IV over 2 hours

Also known as: Mylotarg, GMTZ

Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

mitoxantrone hydrochloride DRUG

Given IV over 1 hour

Also known as: Novantrone, CL 232315, DAD, DHAD, Mitozantrone, NSC #301739

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome; Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome; Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome

Eligibility Criteria

• Age: Up to 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (198)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Banner Desert Medical Center

Mesa, Arizona, 85202, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724-5024, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, 90048-1865, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital Central California

Madera, California, 93636-8762, United States

Location

Children's Hospital and Research Center Oakland

Oakland, California, 94609, United States

Location

Kaiser Permanente Medical Center - Oakland

Oakland, California, 94611, United States

Location

Children's Hospital of Orange County

Orange, California, 92868-3874, United States

Location

Sutter Cancer Center

Sacramento, California, 95816, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123-4282, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Santa Barbara Cottage Children's Hospital

Santa Barbara, California, 93105, United States

Location

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

Torrance, California, 90502, United States

Location

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

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

Farmington, Connecticut, 06360-2875, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

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

Location

Walter Reed Army Medical Center

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

Location

Broward General Medical Center Cancer Center

Fort Lauderdale, Florida, 33316, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207-8426, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Baptist-South Miami Regional Cancer Program

Miami, Florida, 33176, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, 32806, United States

Location

Nemours Children's Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

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

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

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

Savannah, Georgia, 31403-3089, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Tripler Army Medical Center

Tripler AMC, Hawaii, 96859-5000, United States

Location

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

Boise, Idaho, 83712, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612-7243, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453-2699, United States

Location

Keyser Family Cancer Center at Advocate Hope Children's Hospital

Oak Lawn, Illinois, 60453, United States

Location

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, 60068-1174, United States

Location

Simmons Cooper Cancer Institute

Springfield, Illinois, 62794-9677, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

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

Kansas City, Kansas, 66160-7357, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

CancerCare of Maine at Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

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

Portland, Maine, 04102, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

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

Springfield, Massachusetts, 01199-0001, United States

Location

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

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

Ann Arbor, Michigan, 48109-0286, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49008, United States

Location

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, 48910, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Children's Hospital

Omaha, Nebraska, 68114-4113, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, 07503, United States

Location

Overlook Hospital

Summit, New Jersey, 07902, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Albany Medical Center Hospital

Albany, New York, 12208, United States

Location

Brooklyn Hospital Center

Brooklyn, New York, 11201-5493, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11040, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

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

Rochester, New York, 14642, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Mission Hospitals - Memorial Campus

Asheville, North Carolina, 28801, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, 27834, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404, United States

Location

Toledo Hospital

Toledo, Ohio, 43606, United States

Location

Medical University of Ohio Cancer Center

Toledo, Ohio, 43614, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, 97227, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18017, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Penn State Children's Hospital

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, 02903, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, 29203, United States

Location

Greenville Hospital Cancer Center

Greenville, South Carolina, 29605, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

T.C. Thompson Children's Hospital

Chattanooga, Tennessee, 37403, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37916, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, 79106, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

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

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Baylor University Medical Center - Houston

Houston, Texas, 77030, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, 05401, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042-3300, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Naval Medical Center - Portsmouth

Portsmouth, Virginia, 23708-2197, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Carilion Medical Center for Children at Roanoke Community Hospital

Roanoke, Virginia, 24014, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Mary Bridge Children's Hospital and Health Center - Tacoma

Tacoma, Washington, 98405, United States

Location

Madigan Army Medical Center - Tacoma

Tacoma, Washington, 98431, United States

Location

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, 25302, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

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

Milwaukee, Wisconsin, 53226, United States

Location

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Herston, Queensland, 4029, Australia

Location

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Janeway Children's Health and Rehabilitation Centre

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

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Starship Children's Health

Grafton, 1145, New Zealand

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

Swiss Pediatric Oncology Group Bern

Bern, 3010, Switzerland

Location

Swiss Pediatric Oncology Group Geneva

Geneva, 1205, Switzerland

Location

Related Publications (11)

• 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.

  PMID: 22378848 BACKGROUND

• 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.

  PMID: 25092781 RESULT

• 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.

  PMID: 40294366 DERIVED

• 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.

  PMID: 38295280 DERIVED

• 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.

  PMID: 37267439 DERIVED

• 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.

  PMID: 36815378 DERIVED

• 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.

  PMID: 34596937 DERIVED

• 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.

  PMID: 33080007 DERIVED

• 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.

  PMID: 28883080 DERIVED

• 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.

  PMID: 27133823 DERIVED

• 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.

  PMID: 23471307 DERIVED

Related Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

MeSH Terms

Conditions

Leukemia; Congenital Abnormalities; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute

Interventions

Asparaginase; Cytarabine; Daunorubicin; Etoposide; etoposide phosphate; Gemtuzumab; Mitoxantrone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Anthraquinones; Anthrones; Anthracenes; Quinones

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Alan S. Gamis, MD, MPH

  Children's Mercy Hospital Kansas City

  STUDY CHAIR

• Richard Aplenc, MD, MSCE

  Children's Hospital of Philadelphia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2006
• First Posted: September 7, 2006
• Study Start: August 1, 2006
• Primary Completion: August 1, 2013
• Study Completion: September 30, 2020
• Last Updated: March 24, 2021
• Results First Posted: January 13, 2015

Record last verified: 2017-02

Locations

PR (1); CA (11); AU (4); NZ (2); CH (2); US (178)