Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00372593 |
Recruitment Status :
Completed
First Posted : September 7, 2006
Results First Posted : January 13, 2015
Last Update Posted : March 24, 2021
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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 |

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 |

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:
Drug: cytarabine Given IV
Other Names:
Drug: daunorubicin hydrochloride Given IV over 6 hours
Other Names:
Drug: etoposide Given IV over 1-4 hours
Other Names:
Drug: mitoxantrone hydrochloride Given IV over 1 hour
Other Names:
|
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:
Drug: cytarabine Given IV
Other Names:
Drug: daunorubicin hydrochloride Given IV over 6 hours
Other Names:
Drug: etoposide Given IV over 1-4 hours
Other Names:
Drug: gemtuzumab ozogamicin Given IV over 2 hours
Other Names:
Drug: mitoxantrone hydrochloride Given IV over 1 hour
Other Names:
|
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:
Drug: cytarabine Given IV
Other Names:
Drug: daunorubicin hydrochloride Given IV over 6 hours
Other Names:
Drug: etoposide Given IV over 1-4 hours
Other Names:
Drug: mitoxantrone hydrochloride Given IV over 1 hour
Other Names:
|
- 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.
- 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.
- 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.
- 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
- Mortality [ Time Frame: During the first three courses of therapy ]Number of participants who died during the first three courses of therapy.
- 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.
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | up to 29 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00372593

Study Chair: | Alan S. Gamis, MD, MPH | Children's Mercy Hospital Kansas City | |
Study Chair: | Richard Aplenc, MD, MSCE | Children's Hospital of Philadelphia |
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 Key Record Dates |
Results First Posted: | January 13, 2015 |
Last Update Posted: | March 24, 2021 |
Last Verified: | February 2017 |
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) |
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 |