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Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00369317
First received: August 24, 2006
Last updated: July 19, 2012
Last verified: December 2011
History of Changes
  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. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
 Drug: asparaginase
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: thioguanine
 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival from the beginning of the study to the time to induction failure, relapse, or death [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Induction remission rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Percentage of patients that experience grade 3 or 4 toxicity [ Designated as safety issue: Yes ]
  • Prevalence of leukemia phenotype and GATA1 mutations [ Designated as safety issue: No ]
  • Relationship of GATA1 mutations with leukemia phenotype and EFS rates [ Designated as safety issue: No ]
  • Relationship of minimal residual disease monitored by flow cytometry and remission status during and after completion of therapy based on bone marrow morphology [ Designated as safety issue: No ]
  • Parameters of in vitro drug sensitivity and in vivo Ara-C pharmacokinetics [ Designated as safety issue: No ]
  • Gene expression profiles by microarrays and relationship to leukemia phenotype and outcome [ Designated as safety issue: No ]
  • Relationship of functional polymorphisms in phase I and phase II detoxification genes and DNA repair pathways that may modify susceptibility to leukemia and therapy outcome [ Designated as safety issue: No ]
  • Effect of karyotypic abnormalities on survival [ Designated as safety issue: No ]
  • DS leukemia cell bank for future biological studies [ Designated as safety issue: No ]

Estimated Enrollment: 205
Study Start Date: March 2007
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 3 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of Down syndrome (DS) or DS mosaicism by karyotype or chromosomal analysis

  • Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid leukemia (AML)

    • Newly diagnosed disease

  • Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either of the following criteria:

    • At least 30% blasts in the bone marrow regardless of time since resolution of TMD
    • More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow
  • Immunophenotype required for study entry
  • No promyelocytic leukemia

PATIENT CHARACTERISTICS:

  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT < 2.5 times ULN

  • Creatinine adjusted according to age as follows:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male]) OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
  • No evidence of dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry > 94%

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or any antileukemic therapy

    • Intrathecal cytarabine therapy given at diagnosis allowed
  • Prior therapy for TMD allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369317

  Show 159 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Jeffrey Taub, MD Children's Hospital of Michigan
Investigator: Prasad Mathew, MD University of New Mexico Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT00369317     History of Changes
Other Study ID Numbers: CDR0000492776, COG-AAML0431
Study First Received: August 24, 2006
Last Updated: July 19, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
untreated childhood acute myeloid leukemia and other myeloid malignancies
childhood acute minimally differentiated myeloid leukemia (M0)
secondary acute myeloid leukemia
childhood acute basophilic leukemia
childhood acute monocytic leukemia (M5b)
childhood acute eosinophilic leukemia
 childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Down Syndrome
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Neoplasms by Histologic Type
 Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Asparaginase
Cytarabine
Daunorubicin
Etoposide
Thioguanine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013