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

NCT00411281 | Withdrawn Phase 3 DMC

• 3 other identifiers: AAML0532COG-AAML0532CDR0000518352
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Leukemia

Keywords

acute myeloid leukemia/transient myeloproliferative disorder

Outcome Measures

Primary Outcomes (1)

• Event-free survival

Secondary Outcomes (4)

• Overall survival

• Disease-related mortality

• Percentage of patients experiencing grade 3-4 toxicity

• Incidence of subsequent leukemia in patients for whom transient myeloproliferative disorder is resolved

Study Arms (2)

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

Group II

OTHER

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

Procedure: observation

Interventions

cytarabine DRUG

Given subcutaneously

Group I

observation PROCEDURE

No intervention

Group II

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Myeloproliferative Syndrome, Transient

Interventions

Cytarabine; Observation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Methods; Investigative Techniques

Study Officials

• April D. Sorrell, MD

  Rutgers Cancer Institute of New Jersey

  STUDY CHAIR

• Jeffrey Taub, MD

  Children's Hospital of Michigan

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 13, 2006
• Study Start: March 1, 2006
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: September 30, 2015

Record last verified: 2013-08