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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00372593
First received: September 6, 2006
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Leukemia
Drug: asparaginase
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: gemtuzumab ozogamicin
Drug: mitoxantrone hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: Time from study entry to time of induction failure, relapse, or death ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to calculate estimates of 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 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 [ Time Frame: Time from study entry, assessed up to 10 years ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Time from the end of course 3 (Intensification I) to death or relapse; assessed for up to 10 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to calculate estimates DFS. Analysis of DFS of Down syndrome patients will be performed separately.

  • Mortality [ Time Frame: During the first three courses of therapy ] [ Designated as safety issue: No ]
  • Time to marrow recovery [ Time Frame: At 25 days after treatment with Induction I, Induction II, and Intensification I ] [ Designated as safety issue: No ]
  • Toxicities, including infectious complications [ Time Frame: From the time therapy is initiated, assessed up to 10 years ] [ Designated as safety issue: Yes ]

Enrollment: 1070
Study Start Date: August 2006
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (standard therapy)

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 II

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, and 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hour infusion of gemtuzumab ozogamicin on day 6.

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-hour 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-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
Drug: mitoxantrone hydrochloride
Given IV over 1 hour
Other Names:
  • Novantrone
  • CL 232315
  • DAD
  • DHAD
  • Mitozantrone
  • NSC #301739

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
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 -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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372593

  Show 198 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Alan S. Gamis, MD, MPH Children's Mercy Hospital
Study Chair: Richard Aplenc, MD, MSCE Children's Hospital of Philadelphia
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00372593     History of Changes
Other Study ID Numbers: AAML0531, COG-AAML0531, CDR0000487497
Study First Received: September 6, 2006
Last Updated: February 25, 2014
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on August 28, 2014