Low-Dose Cytarabine in Treating Infants With Down Syndrome and Transient Myeloproliferative Disorder - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00411281

Purpose

RATIONALE: Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. Giving low-doses of cytarabine may be an effective treatment for Down syndrome and transient myeloproliferative disorder.

Sometimes the disease may not need treatment until it progresses. In this case, observation may be sufficient.

PURPOSE: This phase III trial is studying low-dose cytarabine to see how well it works in treating infants with Down syndrome and transient myeloproliferative disorder.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Procedure: observation	Phase III

Genetics Home Reference related topics: Down syndrome

MedlinePlus related topics: Down Syndrome Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cytarabine hydrochloride Cytarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	Treatment of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)

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

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Disease-related mortality [ Designated as safety issue: No ]
Percentage of patients experiencing grade 3-4 toxicity [ Designated as safety issue: Yes ]
Incidence of subsequent leukemia in patients for whom transient myeloproliferative disorder is resolved [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	March 2006
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group I: Experimental Patients receive very low-dose cytarabine subcutaneously twice daily on days 1-7. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or complete or hepatic clinical remission undergo observation.	Drug: cytarabine Given subcutaneously
Group II: No Intervention Patients are observed. If symptoms of intermediate- or high-risk disease develop, patients may crossover to group I.	Procedure: observation No intervention

Detailed Description:

OBJECTIVES:

Primary

Determine whether very low-dose cytarabine can improve event-free survival (EFS) rates in infants with high-risk transient myeloproliferative disorder (TMD), using high-risk TMD patients from clinical trial COG-A2971 for historic comparison, and in infants with intermediate-risk TMD, using intermediate-risk TMD patients from clinical trial COG-A2971 for historic comparison.
Maintain the current high overall EFS rate in low-risk TMD patients.

Secondary

Assess the toxicity of this regimen in these patients.

OUTLINE: This is a nonrandomized, multicenter, crossover study. Patients are stratified according to disease risk (high or intermediate vs low).

Group I (patients with high- or intermediate-risk transient myeloproliferative disorder [TMD]): Patients receive very low-dose cytarabine subcutaneously twice daily on days 1-7. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or complete or hepatic clinical remission undergo observation.
Group II (patients with low-risk TMD): Patients are observed. If symptoms of intermediate- or high-risk disease develop, patients may crossover to group I. After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of transient myeloproliferative disorder (TMD)
Diagnosis of Down syndrome or Down syndrome mosaicism (confirmed by karyotype analysis within the past 3 weeks) AND 1 of the following:
- Nonerythroid and nonlymphoid blasts (any amount) in the peripheral blood with verification of a second sample
- Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including > 5% nonerythroid/nonlymphoid blasts documented by bone marrow aspirate or biopsy)
Immunophenotype characterization required
High-, intermediate-, or low-risk TMD, as defined by the following:
- High-risk TMD, meeting 1 of the following criteria:
  - Life-threatening cardio-respiratory compromise due to complications of TMD (e.g., organomegaly or effusions)
    - Life-threatening cardio-respiratory compromise is defined as cardiovascular grade 4 edema, grade 4 pericardial effusions, or grade 4 pleural effusions
  - Hyperleukocytosis, defined as a WBC > 100,000/mm³
  - Any degree of hepatomegaly (palpable on physical exam) combined with life-threatening hepatic dysfunction
    - Life-threatening hepatic dysfunction is defined as grade 4 disseminated intravascular coagulation, grade 4 ascites, grade 4 bilirubin (> 10.0 times upper limit of normal [ULN]), or grade 4 AST or ALT (> 20.0 times ULN)
- Intermediate-risk TMD, meeting all of the following criteria:
  - Hepatomegaly (palpable on physical exam) combined with nonlife-threatening hepatic dysfunction (i.e., grade 1-3 hepatic dysfunction [AST or ALT ≤ 2.5 times ULN] and/or a total or direct bilirubin ≤ 1.5 times ULN)
  - No evidence of life-threatening cardiovascular, respiratory, or hepatic compromise due to complications of TMD
- Low-risk TMD, meeting all of the following criteria:
  - No palpable hepatomegaly on physical exam OR hepatomegaly is present without hepatic dysfunction (i.e., grade 0 hepatic dysfunction)
  - No evidence of life-threatening cardiovascular, respiratory, or hepatic compromise due to complications of TMD

PATIENT CHARACTERISTICS:

See Disease Characteristics
No biliary atresia by hepatic ultrasound for patients with bilirubin 3.0-10.0 times ULN

PRIOR CONCURRENT THERAPY:

No prior antileukemic therapy (except for leukapheresis or exchange transfusion)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411281

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	April D. Sorrell, MD	Cancer Institute of New Jersey
Investigator:	Jeffrey Taub, MD	Children's Hospital of Michigan

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

Study ID Numbers:	CDR0000518352, COG-AAML0532
Study First Received:	December 11, 2006
Last Updated:	January 30, 2009
ClinicalTrials.gov Identifier:	NCT00411281 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

acute myeloid leukemia/transient myeloproliferative disorder

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Hematologic Diseases
Myeloproliferative Disorders
Chromosome Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Immunosuppressive Agents
Antiviral Agents
Mental Retardation

Leukemia
Acute Myelocytic Leukemia
Genetic Diseases, Inborn
Abnormalities, Multiple
Neurologic Manifestations
Down Syndrome
Congenital Abnormalities
Bone Marrow Diseases
Neurobehavioral Manifestations
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia
Therapeutic Uses
Abnormalities, Multiple
Congenital Abnormalities
Neurobehavioral Manifestations
Cytarabine
Neoplasms by Histologic Type

Hematologic Diseases
Nervous System Diseases
Chromosome Disorders
Myeloproliferative Disorders
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Mental Retardation
Neoplasms
Genetic Diseases, Inborn
Neurologic Manifestations
Down Syndrome
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 06, 2009