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Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: March 20, 2009
Last updated: April 12, 2016
Last verified: April 2016
This phase III trial is studying combination chemotherapy to see how well it works in treating young patients with newly diagnosed acute promyelocytic leukemia. 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. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Condition Intervention Phase
Childhood Acute Promyelocytic Leukemia (M3)
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Drug: arsenic trioxide
Drug: mitoxantrone hydrochloride
Other: diagnostic laboratory biomarker analysis
Drug: idarubicin
Drug: tretinoin
Drug: cytarabine
Drug: mercaptopurine tablet
Drug: methotrexate
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® IND# 103, 331) During Consolidation

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 on study to failure to achieve hematological CR afterConsolidation 1, relapse, or death, assessed up to 10 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the EFS of children enrolled on AAML0631 separately for each risk group.

Secondary Outcome Measures:
  • Hematologic, molecular, and cytogenetic remission rates after each phase of therapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be used to estimate OS separately for each risk group.

Enrollment: 108
Study Start Date: March 2009
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
See Detailed Description
Drug: arsenic trioxide
Given IV
Other Names:
  • Arsenic (III) Oxide
  • Arsenic Sesquioxide
  • Arsenous Acid Anhydride
  • AS2O3
  • Trisenox
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Novantrone
Other: diagnostic laboratory biomarker analysis
Correlative studies
Drug: idarubicin
Given IV
Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
Drug: tretinoin
Given orally
Other Names:
  • ATRA
  • Retin-A
  • TRA
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: mercaptopurine tablet
Given orally
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: methotrexate
Given orally
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

  Show Detailed Description


Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must be newly diagnosed with a clinical diagnosis of acute promyelocytic leukemia initially by morphology (bone marrow or peripheral blood); bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted; APL is considered a hematological emergency and treatment should be initiated as quickly as possible without waiting for molecular or cytogenetic/fluorescence in situ hybridization (FISH) confirmation; for patients who are unable to begin receiving ATRA in a timely manner following a presumed diagnosis of APL, consideration should be given to initiating ATRA and proceeding with treatment outside of the AAML0631 protocol; if the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate PML-RARA and/or RARA-PML transcripts by RQ-PCR to be eligible; patients without evidence of APL by bone marrow or peripheral blood morphology but with isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible provided that the t(15;17) translocation is documented on either marrow or tumor tissue by cytogenetics, FISH, or PCR prior to study enrollment; in this situation, touch preps from the tumor site can be evaluated by FISH with PML-RARA probes; NOTE: A lumbar puncture is not required to be enrolled on study; if the diagnosis of APL is known or suspected, extreme caution must be exercised in performing a lumbar puncture during active coagulopathy; in addition a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma if central nervous system (CNS) disease is suspected or proven; if CNS disease is documented, patients are still eligible
  • No minimal performance status criteria
  • The patient must not have received systemic definitive treatment for APL or other suspected leukemia, including cytotoxic chemotherapy, retinoids, or arsenic; prior therapy with corticosteroids, hydroxyurea, or leukopheresis will not exclude the patient; if a patient received intrathecal cytarabine prior to the diagnosis of APL being known, the patient will still be eligible as long as they meet all other eligibility requirements

Exclusion Criteria:

  • Pregnant women or nursing mothers are excluded; treatment under this protocol would expose an unborn child to significant risks; patients should not be pregnant or plan to become pregnant while on treatment; women and men of reproductive potential should agree to use an effective means of birth control; there is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount even for short periods
  • Patients with a pre-existing prolonged QT Syndrome will not be eligible for this protocol due to the use of arsenic trioxide which can prolong the QT interval
  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 identifier: NCT00866918

  Show 111 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: John Gregory, MD Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group Identifier: NCT00866918     History of Changes
Other Study ID Numbers: AAML0631  NCI-2011-01904  CDR0000637184  AAML0631  AAML0631  U10CA098543 
Study First Received: March 20, 2009
Last Updated: April 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Arsenic trioxide
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Sensory System Agents processed this record on September 30, 2016