Back to resultsLow-Dose Cytarabine in Treating Infants With Down Syndrome and Transient Myeloproliferative Disorder
Primary Purpose
Leukemia
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
cytarabine
observation
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring acute myeloid leukemia/transient myeloproliferative disorder
Eligibility 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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Group I
Group II
Arm Description
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.
Patients are observed. If symptoms of intermediate- or high-risk disease develop, patients may crossover to group I.
Outcomes
Primary Outcome Measures
Event-free survival
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00411281
First Posted
December 11, 2006
Last Updated
September 28, 2015
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00411281
Brief Title
Low-Dose Cytarabine in Treating Infants With Down Syndrome and Transient Myeloproliferative Disorder
Official Title
Treatment of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2013
Overall Recruitment Status
Withdrawn
Why Stopped
Per Group Chair: This study will not move forward.
Study Start Date
March 2006 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
November 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
acute myeloid leukemia/transient myeloproliferative disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group I
Arm Type
Experimental
Arm Description
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.
Arm Title
Group II
Arm Type
Other
Arm Description
Patients are observed. If symptoms of intermediate- or high-risk disease develop, patients may crossover to group I.
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
Given subcutaneously
Intervention Type
Procedure
Intervention Name(s)
observation
Intervention Description
No intervention
Primary Outcome Measure Information:
Title
Event-free survival
Secondary Outcome Measure Information:
Title
Overall survival
Title
Disease-related mortality
Title
Percentage of patients experiencing grade 3-4 toxicity
Title
Incidence of subsequent leukemia in patients for whom transient myeloproliferative disorder is resolved
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
April D. Sorrell, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jeffrey Taub, MD
Organizational Affiliation
Children's Hospital of Michigan
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
Low-Dose Cytarabine in Treating Infants With Down Syndrome and Transient Myeloproliferative Disorder
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