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

This study has been withdrawn prior to enrollment.
(Per Group Chair: This study will not move forward.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00411281
First received: December 11, 2006
Last updated: August 22, 2013
Last verified: August 2013
  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 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)

Resource links provided by NLM:


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

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 ]

Enrollment: 0
Study Start Date: March 2006
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I
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
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 non life-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
Investigators
Study Chair: April D. Sorrell, MD Rutgers Cancer Institute of New Jersey
Study Chair: Jeffrey Taub, MD Children's Hospital of Michigan
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00411281     History of Changes
Other Study ID Numbers: AAML0532, COG-AAML0532, CDR0000518352
Study First Received: December 11, 2006
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
acute myeloid leukemia/transient myeloproliferative disorder

Additional relevant MeSH terms:
Down Syndrome
Leukemia
Myeloproliferative Disorders
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
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014