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

NCT ID: NCT00372593

Last Updated: 2021-03-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1070 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2020-09-30

Brief Summary

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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.

Detailed Description

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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

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Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type ACTIVE_COMPARATOR

asparaginase

Intervention Type DRUG

Given intramuscularly

cytarabine

Intervention Type DRUG

Given IV

daunorubicin hydrochloride

Intervention Type DRUG

Given IV over 6 hours

etoposide

Intervention Type DRUG

Given IV over 1-4 hours

mitoxantrone hydrochloride

Intervention Type DRUG

Given IV over 1 hour

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

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.

Group Type EXPERIMENTAL

asparaginase

Intervention Type DRUG

Given intramuscularly

cytarabine

Intervention Type DRUG

Given IV

daunorubicin hydrochloride

Intervention Type DRUG

Given IV over 6 hours

etoposide

Intervention Type DRUG

Given IV over 1-4 hours

gemtuzumab ozogamicin

Intervention Type DRUG

Given IV over 2 hours

mitoxantrone hydrochloride

Intervention Type DRUG

Given IV over 1 hour

Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome

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.

Group Type ACTIVE_COMPARATOR

asparaginase

Intervention Type DRUG

Given intramuscularly

cytarabine

Intervention Type DRUG

Given IV

daunorubicin hydrochloride

Intervention Type DRUG

Given IV over 6 hours

etoposide

Intervention Type DRUG

Given IV over 1-4 hours

mitoxantrone hydrochloride

Intervention Type DRUG

Given IV over 1 hour

Interventions

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asparaginase

Given intramuscularly

Intervention Type DRUG

cytarabine

Given IV

Intervention Type DRUG

daunorubicin hydrochloride

Given IV over 6 hours

Intervention Type DRUG

etoposide

Given IV over 1-4 hours

Intervention Type DRUG

gemtuzumab ozogamicin

Given IV over 2 hours

Intervention Type DRUG

mitoxantrone hydrochloride

Given IV over 1 hour

Intervention Type DRUG

Other Intervention Names

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E.coli E.coli L-asparaginase EC 3.5.2.2 colaspase L-asnase Elspar Kidrolase Crasnitin Leunase NSC 109229 Cytosine arabinoside Ara-C Cytosar NSC # 63878 Daunomycin rubidomycin Cerubidine NSC #82151 VePesid Etopophos VP-16 NSC #141540 Mylotarg GMTZ Novantrone CL 232315 DAD DHAD Mitozantrone NSC #301739

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

29 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan S. Gamis, MD, MPH

Role: STUDY_CHAIR

Children's Mercy Hospital Kansas City

Richard Aplenc, MD, MSCE

Role: STUDY_CHAIR

Children's Hospital of Philadelphia

Locations

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UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Site Status

Banner Desert Medical Center

Mesa, Arizona, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Children's Hospital and Research Center Oakland

Oakland, California, United States

Site Status

Kaiser Permanente Medical Center - Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Santa Barbara Cottage Children's Hospital

Santa Barbara, California, United States

Site Status

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

Torrance, California, United States

Site Status

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, United States

Site Status

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

Farmington, Connecticut, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Broward General Medical Center Cancer Center

Fort Lauderdale, Florida, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

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

Tampa, Florida, United States

Site Status

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

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

Atlanta, Georgia, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

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

Savannah, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Tripler Army Medical Center

Tripler AMC, Hawaii, United States

Site Status

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

Boise, Idaho, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

Keyser Family Cancer Center at Advocate Hope Children's Hospital

Oak Lawn, Illinois, United States

Site Status

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, United States

Site Status

Simmons Cooper Cancer Institute

Springfield, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

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

Kansas City, Kansas, United States

Site Status

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States

Site Status

Children's Hospital of New Orleans

New Orleans, Louisiana, United States

Site Status

CancerCare of Maine at Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

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

Portland, Maine, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

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

Boston, Massachusetts, United States

Site Status

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

Springfield, Massachusetts, United States

Site Status

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, United States

Site Status

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

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

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

Grosse Pointe Woods, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Children's Hospital

Omaha, Nebraska, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

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

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Albany Medical Center Hospital

Albany, New York, United States

Site Status

Brooklyn Hospital Center

Brooklyn, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

Schneider Children's Hospital

New Hyde Park, New York, United States

Site Status

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

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

Rochester, New York, United States

Site Status

Stony Brook University Cancer Center

Stony Brook, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

CCOP - MeritCare Hospital

Fargo, North Dakota, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Toledo Hospital

Toledo, Ohio, United States

Site Status

Medical University of Ohio Cancer Center

Toledo, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, United States

Site Status

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States

Site Status

Greenville Hospital Cancer Center

Greenville, South Carolina, United States

Site Status

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Site Status

T.C. Thompson Children's Hospital

Chattanooga, Tennessee, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

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

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Baylor University Medical Center - Houston

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Carilion Medical Center for Children at Roanoke Community Hospital

Roanoke, Virginia, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

Mary Bridge Children's Hospital and Health Center - Tacoma

Tacoma, Washington, United States

Site Status

Madigan Army Medical Center - Tacoma

Tacoma, Washington, United States

Site Status

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

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

Milwaukee, Wisconsin, United States

Site Status

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Children's Hospital

Herston, Queensland, Australia

Site Status

Women's and Children's Hospital

North Adelaide, South Australia, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Janeway Children's Health and Rehabilitation Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Children's Hospital of Western Ontario

London, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Starship Children's Health

Grafton, , New Zealand

Site Status

San Jorge Children's Hospital

Santurce, , Puerto Rico

Site Status

Swiss Pediatric Oncology Group Bern

Bern, , Switzerland

Site Status

Swiss Pediatric Oncology Group Geneva

Geneva, , Switzerland

Site Status

Countries

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United States Australia Canada New Zealand Puerto Rico Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 22378848 (View on PubMed)

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.

Reference Type RESULT
PMID: 25092781 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40294366 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38295280 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37267439 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36815378 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34596937 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33080007 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28883080 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27133823 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23471307 (View on PubMed)

Related Links

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https://nctn-data-archive.nci.nih.gov/

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

Other Identifiers

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COG-AAML0531

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000487497

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00320

Identifier Type: REGISTRY

Identifier Source: secondary_id

AAML0531

Identifier Type: -

Identifier Source: org_study_id

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