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

• ClinicalTrials.gov Identifier: NCT00372593
• Recruitment Status: Completed
• First Posted: September 7, 2006
• Results First Posted: January 13, 2015
• Last Update Posted: March 24, 2021
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: gemtuzumab ozogamicin; Drug: mitoxantrone hydrochloride	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1070 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: August 2006
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: September 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: asparaginase; Given intramuscularly; Other Names: E.coli; E.coli L-asparaginase; EC 3.5.2.2; colaspase; L-asnase; Elspar; Kidrolase; Crasnitin; Leunase; NSC 109229; Drug: cytarabine; Given IV; Other Names: Cytosine arabinoside; Ara-C; Cytosar; NSC # 63878; Drug: daunorubicin hydrochloride; Given IV over 6 hours; Other Names: Daunomycin; rubidomycin; Cerubidine; NSC #82151; Drug: etoposide; Given IV over 1-4 hours; Other Names: VePesid; Etopophos; VP-16; NSC #141540; Drug: mitoxantrone hydrochloride; Given IV over 1 hour; Other Names: Novantrone; CL 232315; DAD; DHAD; Mitozantrone; NSC #301739
Experimental: 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.	Drug: asparaginase; Given intramuscularly; Other Names: E.coli; E.coli L-asparaginase; EC 3.5.2.2; colaspase; L-asnase; Elspar; Kidrolase; Crasnitin; Leunase; NSC 109229; Drug: cytarabine; Given IV; Other Names: Cytosine arabinoside; Ara-C; Cytosar; NSC # 63878; Drug: daunorubicin hydrochloride; Given IV over 6 hours; Other Names: Daunomycin; rubidomycin; Cerubidine; NSC #82151; Drug: etoposide; Given IV over 1-4 hours; Other Names: VePesid; Etopophos; VP-16; NSC #141540; Drug: gemtuzumab ozogamicin; Given IV over 2 hours; Other Names: Mylotarg; GMTZ; Drug: mitoxantrone hydrochloride; Given IV over 1 hour; Other Names: Novantrone; CL 232315; DAD; DHAD; Mitozantrone; NSC #301739
Active Comparator: 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.	Drug: asparaginase; Given intramuscularly; Other Names: E.coli; E.coli L-asparaginase; EC 3.5.2.2; colaspase; L-asnase; Elspar; Kidrolase; Crasnitin; Leunase; NSC 109229; Drug: cytarabine; Given IV; Other Names: Cytosine arabinoside; Ara-C; Cytosar; NSC # 63878; Drug: daunorubicin hydrochloride; Given IV over 6 hours; Other Names: Daunomycin; rubidomycin; Cerubidine; NSC #82151; Drug: etoposide; Given IV over 1-4 hours; Other Names: VePesid; Etopophos; VP-16; NSC #141540; Drug: mitoxantrone hydrochloride; Given IV over 1 hour; Other Names: Novantrone; CL 232315; DAD; DHAD; Mitozantrone; NSC #301739

Outcome Measures

Primary Outcome Measures :

1. 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 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.
2. Overall Survival at 3 Years [ Time Frame: Time from study entry, assessed 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.

Secondary Outcome Measures :

1. Remission Induction Rate After 2 Courses of Induction Therapy [ Time Frame: After 2 courses of induction (I and II) therapy, assessed for up to 10 years ]
   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.
2. Disease-free Survival (DFS) [ Time Frame: At 3 years from end of Intensification I ]
   Time from end of Intensification I to relapse, death or last contact
3. Mortality [ Time Frame: During the first three courses of therapy ]
   Number of participants who died during the first three courses of therapy.
4. Time to Marrow Recovery [ Time Frame: At 25 days after treatment with Induction I, Induction II, and Intensification I ]
   Mean time to ANC recovery - defined as ANC greater than 500/MicroLiter for 3 consecutive days.
5. Toxicities, Including Infectious Complications [ Time Frame: From the time therapy is initiated, assessed up to 10 years ]
   Number of participants with at least one grade 3 or higher adverse event during therapy.

Eligibility Criteria

• Ages Eligible for Study: up to 29 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States, 35294

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States, 36604

United States, Arizona

Banner Desert Medical Center

Mesa, Arizona, United States, 85202

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States, 85724-5024

United States, Arkansas

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Southern California Permanente Medical Group

Downey, California, United States, 90242

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010-3000

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States, 92354

Childrens Hospital Los Angeles

Los Angeles, California, United States, 90027

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048-1865

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States, 90095-1781

Children's Hospital Central California

Madera, California, United States, 93636-8762

Children's Hospital and Research Center Oakland

Oakland, California, United States, 94609

Kaiser Permanente Medical Center - Oakland

Oakland, California, United States, 94611

Children's Hospital of Orange County

Orange, California, United States, 92868-3874

Sutter Cancer Center

Sacramento, California, United States, 95816

University of California Davis Cancer Center

Sacramento, California, United States, 95817

Rady Children's Hospital - San Diego

San Diego, California, United States, 92123-4282

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94115

Santa Barbara Cottage Children's Hospital

Santa Barbara, California, United States, 93105

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

Torrance, California, United States, 90502

United States, Colorado

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, United States, 80045

United States, Connecticut

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

Farmington, Connecticut, United States, 06360-2875

Yale Cancer Center

New Haven, Connecticut, United States, 06520-8028

United States, Delaware

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States, 19803

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010-2970

Walter Reed Army Medical Center

Washington, District of Columbia, United States, 20307-5001

United States, Florida

Broward General Medical Center Cancer Center

Fort Lauderdale, Florida, United States, 33316

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States, 33901

University of Florida Shands Cancer Center

Gainesville, Florida, United States, 32610-0232

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, United States, 33021

Nemours Children's Clinic

Jacksonville, Florida, United States, 32207-8426

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States, 33136

Miami Children's Hospital

Miami, Florida, United States, 33155

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States, 33176

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States, 32803-1273

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, United States, 32806

Nemours Children's Clinic - Orlando

Orlando, Florida, United States, 32806

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States, 32504

All Children's Hospital

Saint Petersburg, Florida, United States, 33701

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

Tampa, Florida, United States, 33607

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States, 33407

United States, Georgia

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

Atlanta, Georgia, United States, 30322

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States, 30322

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, United States, 30912

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

Savannah, Georgia, United States, 31403-3089

United States, Hawaii

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States, 96813

Tripler Army Medical Center

Tripler AMC, Hawaii, United States, 96859-5000

United States, Idaho

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

Boise, Idaho, United States, 83712

United States, Illinois

University of Illinois Cancer Center

Chicago, Illinois, United States, 60612-7243

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States, 60614

University of Chicago Cancer Research Center

Chicago, Illinois, United States, 60637-1470

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States, 60153

Advocate Christ Medical Center

Oak Lawn, Illinois, United States, 60453-2699

Keyser Family Cancer Center at Advocate Hope Children's Hospital

Oak Lawn, Illinois, United States, 60453

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, United States, 60068-1174

Simmons Cooper Cancer Institute

Springfield, Illinois, United States, 62794-9677

United States, Indiana

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202-5289

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States, 46260

United States, Iowa

Blank Children's Hospital

Des Moines, Iowa, United States, 50309

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States, 52242-1002

United States, Kansas

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

Kansas City, Kansas, United States, 66160-7357

United States, Kentucky

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States, 40536-0093

Kosair Children's Hospital

Louisville, Kentucky, United States, 40232

United States, Louisiana

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States, 71315-3198

Children's Hospital of New Orleans

New Orleans, Louisiana, United States, 70118

United States, Maine

CancerCare of Maine at Eastern Maine Medical Center

Bangor, Maine, United States, 04401

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

Portland, Maine, United States, 04102

United States, Maryland

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States, 21215

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231-2410

United States, Massachusetts

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States, 02111

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

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

Boston, Massachusetts, United States, 02115

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

Springfield, Massachusetts, United States, 01199-0001

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, United States, 01655

United States, Michigan

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

Ann Arbor, Michigan, United States, 48109-0286

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201-1379

Hurley Medical Center

Flint, Michigan, United States, 48503

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States, 49503

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

Grosse Pointe Woods, Michigan, United States, 48236

CCOP - Kalamazoo

Kalamazoo, Michigan, United States, 49008

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, United States, 48910

United States, Minnesota

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States, 55404

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States, 55455

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

United States, Mississippi

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States, 39216

United States, Missouri

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States, 65203

Children's Mercy Hospital

Kansas City, Missouri, United States, 64108

Cardinal Glennon Children's Hospital

Saint Louis, Missouri, United States, 63104

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Children's Hospital

Omaha, Nebraska, United States, 68114-4113

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198-6805

United States, Nevada

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States, 89106

United States, New Hampshire

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756-0002

United States, New Jersey

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States, 07601

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

New Brunswick, New Jersey, United States, 08903

Newark Beth Israel Medical Center

Newark, New Jersey, United States, 07112

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States, 07503

Overlook Hospital

Summit, New Jersey, United States, 07902

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131-5636

United States, New York

Albany Medical Center Hospital

Albany, New York, United States, 12208

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Bronx, New York, United States, 10461

Brooklyn Hospital Center

Brooklyn, New York, United States, 11201-5493

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

Winthrop University Hospital

Mineola, New York, United States, 11501

Schneider Children's Hospital

New Hyde Park, New York, United States, 11040

NYU Cancer Institute at New York University Medical Center

New York, New York, United States, 10016

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States, 10021

Mount Sinai Medical Center

New York, New York, United States, 10029

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States, 10032

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

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

Rochester, New York, United States, 14642

Stony Brook University Cancer Center

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

SUNY Upstate Medical University Hospital

Syracuse, New York, United States, 13210

United States, North Carolina

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States, 28801

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

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

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States, 28232-2861

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States, 28233-3549

Duke Comprehensive Cancer Center

Durham, North Carolina, United States, 27710

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, United States, 27834

Wake Forest University Comprehensive Cancer Center

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

United States, North Dakota

CCOP - MeritCare Hospital

Fargo, North Dakota, United States, 58122

United States, Ohio

Akron Children's Hospital

Akron, Ohio, United States, 44308-1062

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229-3039

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States, 44106

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44195

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205-2696

Children's Medical Center - Dayton

Dayton, Ohio, United States, 45404

Toledo Hospital

Toledo, Ohio, United States, 43606

Medical University of Ohio Cancer Center

Toledo, Ohio, United States, 43614

United States, Oklahoma

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, United States, 97227

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States, 97239-3098

United States, Pennsylvania

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States, 18017

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States, 17822-0001

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033-0850

Penn State Children's Hospital

Hershey, Pennsylvania, United States, 17033-0850

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States, 19134-1095

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

United States, Rhode Island

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States, 02903

United States, South Carolina

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States, 29203

Greenville Hospital Cancer Center

Greenville, South Carolina, United States, 29605

United States, South Dakota

Sanford Cancer Center at Sanford USD Medical Center

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

United States, Tennessee

T.C. Thompson Children's Hospital

Chattanooga, Tennessee, United States, 37403

East Tennessee Children's Hospital

Knoxville, Tennessee, United States, 37916

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232-6838

United States, Texas

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, United States, 79106

Dell Children's Medical Center of Central Texas

Austin, Texas, United States, 78723

Driscoll Children's Hospital

Corpus Christi, Texas, United States, 78411

Medical City Dallas Hospital

Dallas, Texas, United States, 75230

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

Dallas, Texas, United States, 75390

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States, 76104

Baylor University Medical Center - Houston

Houston, Texas, United States, 77030

Covenant Children's Hospital

Lubbock, Texas, United States, 79410

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229-3900

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States, 78229-3993

CCOP - Scott and White Hospital

Temple, Texas, United States, 76508

United States, Utah

Primary Children's Medical Center

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

United States, Vermont

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States, 05401

United States, Virginia

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22908

Inova Fairfax Hospital

Falls Church, Virginia, United States, 22042-3300

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States, 23507

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States, 23708-2197

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States, 23298-0037

Carilion Medical Center for Children at Roanoke Community Hospital

Roanoke, Virginia, United States, 24014

United States, Washington

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States, 98105

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States, 99204

Mary Bridge Children's Hospital and Health Center - Tacoma

Tacoma, Washington, United States, 98405

Madigan Army Medical Center - Tacoma

Tacoma, Washington, United States, 98431

United States, West Virginia

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, United States, 25302

United States, Wisconsin

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States, 54307-3508

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States, 53792-6164

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States, 54449

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

Milwaukee, Wisconsin, United States, 53226

Australia, New South Wales

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Royal Children's Hospital

Herston, Queensland, Australia, 4029

Australia, South Australia

Women's and Children's Hospital

North Adelaide, South Australia, Australia, 5006

Australia, Western Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia, 6001

Canada, British Columbia

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada, V6H 3V4

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Newfoundland and Labrador

Janeway Children's Health and Rehabilitation Centre

Saint John's, Newfoundland and Labrador, Canada, A1B 3V6

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Ontario

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8N 3Z5

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada, K7L 5P9

Children's Hospital of Western Ontario

London, Ontario, Canada, N6A 5W9

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

Hospital for Sick Children

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

Hopital Sainte Justine

Montreal, Quebec, Canada, H3T 1C5

Canada

Centre Hospitalier Universitaire de Quebec

Quebec, Canada, G1V 4G2

New Zealand

Christchurch Hospital

Christchurch, New Zealand, 8011

Starship Children's Health

Grafton, New Zealand, 1145

Puerto Rico

San Jorge Children's Hospital

Santurce, Puerto Rico, 00912

Switzerland

Swiss Pediatric Oncology Group Bern

Bern, Switzerland, 3010

Swiss Pediatric Oncology Group Geneva

Geneva, Switzerland, 1205

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Study Chair: Alan S. Gamis, MD, MPH; Children's Mercy Hospital Kansas City
• Study Chair: Richard Aplenc, MD, MSCE; Children's Hospital of Philadelphia

More Information

Additional Information:

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

Publications of Results:

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.

Other 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00372593
• Other Study ID Numbers: AAML0531; COG-AAML0531 ( Other Identifier: Children's Oncology Group ); CDR0000487497 ( Other Identifier: Clinical Trials.gov ); NCI-2009-00320 ( Registry Identifier: Clinical Trials Reporting Program )
• First Posted: September 7, 2006
• Results First Posted: January 13, 2015
• Last Update Posted: March 24, 2021
• Last Verified: February 2017

Keywords provided by Children's Oncology Group:

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)

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cytarabine; Etoposide; Daunorubicin; Mitoxantrone; Asparaginase; Gemtuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antibiotics, Antineoplastic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Antineoplastic Agents, Immunological