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

NCT ID: NCT00411281

Last Updated: 2015-09-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2007-11-30

Brief Summary

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Given subcutaneously

Group II

Patients are observed. If symptoms of intermediate- or high-risk disease develop, patients may crossover to group I.

Group Type: OTHER

observation

Intervention Type: PROCEDURE

No intervention

Interventions

cytarabine

Given subcutaneously

Intervention Type: DRUG

observation

No intervention

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

April D. Sorrell, MD

Role: STUDY_CHAIR

Rutgers Cancer Institute of New Jersey

Jeffrey Taub, MD

Role: STUDY_CHAIR

Children's Hospital of Michigan

Other Identifiers

COG-AAML0532

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000518352

Identifier Type: OTHER

Identifier Source: secondary_id

AAML0532

Identifier Type: -

Identifier Source: org_study_id