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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00369317

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 III

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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:

Genetics Home Reference related topics: Down syndrome

MedlinePlus related topics: Cancer Down Syndrome Leukemia, Childhood

Drug Information available for: Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Etoposide Etoposide phosphate Cytarabine Thioguanine L-Asparaginase

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:	August 2010 (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 in association with myelodysplastic changes
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 141 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

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:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000492776, COG-AAML0431
Study First Received:	August 24, 2006
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00369317 History of Changes
Health Authority:	Unspecified

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:

Antimetabolites
Anti-Infective Agents
Daunorubicin
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses

Syndrome
Abnormalities, Multiple
Congenital Abnormalities
Etoposide
Neurobehavioral Manifestations
Cytarabine
Asparaginase
Neoplasms by Histologic Type
Disease
Hematologic Diseases
Thioguanine
Nervous System Diseases
Myelodysplastic Syndromes
Chromosome Disorders
Leukemia, Myeloid

ClinicalTrials.gov processed this record on February 08, 2010