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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00369317
Registration number
NCT00369317
Ethics application status
Date submitted
24/08/2006
Date registered
29/08/2006
Date last updated
28/01/2022
Titles & IDs
Public title
Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
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Scientific title
The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years
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Secondary ID [1]
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NCI-2009-00318
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Secondary ID [2]
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AAML0431
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Childhood Acute Basophilic Leukemia
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Childhood Acute Eosinophilic Leukemia
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Childhood Acute Erythroleukemia (M6)
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Childhood Acute Megakaryocytic Leukemia (M7)
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Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
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Childhood Acute Monoblastic Leukemia (M5a)
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Childhood Acute Monocytic Leukemia (M5b)
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Childhood Acute Myeloblastic Leukemia With Maturation (M2)
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Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
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Childhood Acute Myelomonocytic Leukemia (M4)
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Childhood Myelodysplastic Syndromes
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de Novo Myelodysplastic Syndromes
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Secondary Acute Myeloid Leukemia
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Secondary Myelodysplastic Syndromes
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Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Blood
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Haematological diseases
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Human Genetics and Inherited Disorders
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Down's syndrome
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Blood
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Other blood disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - asparaginase
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - cytarabine
Treatment: Drugs - thioguanine
Treatment: Drugs - etoposide
Other interventions - laboratory biomarker analysis
Experimental: Treatment (combination chemotherapy) - INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Treatment: Drugs: asparaginase
Given IM
Treatment: Drugs: daunorubicin hydrochloride
Given IV
Treatment: Drugs: cytarabine
Given IV or IT
Treatment: Drugs: thioguanine
Given orally
Treatment: Drugs: etoposide
Given IV
Other interventions: laboratory biomarker analysis
Correlative studies
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Event-free Survival (EFS) at 3 Years
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Assessment method [1]
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Timepoint [1]
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Time from study entry to induction failure, relapse, or death assessed at 3 years.
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Primary outcome [2]
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Overall Survival (OS) at 3 Years
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Assessment method [2]
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Timepoint [2]
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Time from study entry to death, assessed at 3 years.
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Secondary outcome [1]
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Induction Remission Rate
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Assessment method [1]
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Proportion of participants with a remission after four courses of Induction therapy.
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Timepoint [1]
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End of induction therapy (day 112)
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Secondary outcome [2]
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Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
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Assessment method [2]
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Proportion of participants with at least one grade 3 or higher adverse event during therapy.
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Timepoint [2]
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From the beginning of induction therapy to the end of intensification therapy
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Secondary outcome [3]
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Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry
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Assessment method [3]
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Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available.
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Timepoint [3]
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At the start of therapy
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Secondary outcome [4]
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Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis
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Assessment method [4]
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Proportion of participants having GATA1 mutation among patients with phenotype data available.
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Timepoint [4]
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At baseline and at the end of therapy (intensification) or disease relapse
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Secondary outcome [5]
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Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry
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Assessment method [5]
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Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment.
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Timepoint [5]
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After Induction I therapy (day 28 from start of therapy)
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Secondary outcome [6]
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Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
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Assessment method [6]
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Mean and standard deviation of peak plasma concentration. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
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Timepoint [6]
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Days 1, 2, 8, and 9 of induction II
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Secondary outcome [7]
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Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
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Assessment method [7]
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Mean and standard deviation of area under the concentration time curve. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
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Timepoint [7]
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Days 1, 2, 8, and 9 of induction II
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Secondary outcome [8]
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Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
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Assessment method [8]
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Mean and standard deviation of half-life of elimination. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
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Timepoint [8]
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Days 1, 2, 8, and 9 of induction II
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Secondary outcome [9]
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Gene Expression Profiles by Microarrays
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Assessment method [9]
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A hierarchical clustering algorithm is used to assemble the genes into a dendrogram or tree structure with branches containing genes with similar patterns of expression. This ordered representation can be graphically displayed with colors that reflect the qualitative and quantitative relationships of the expressed genes.
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Timepoint [9]
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At baseline and at the time of relapse (if available)
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Eligibility
Key inclusion criteria
- Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
- Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid
leukemia (AML)
- Newly diagnosed disease
- Patients with a history of transient myeloproliferative disorder (TMD) are eligible
provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either
of the following criteria:
- At least 30% blasts in the bone marrow regardless of time since resolution of TMD
- More than 8 weeks since resolution of TMD with = 5% blasts in the bone marrow
- Immunophenotype required for study entry
- No promyelocytic leukemia
- Shortening fraction = 27% by echocardiogram OR ejection fraction = 50% by radionuclide
angiogram
- Bilirubin = 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Creatinine adjusted according to age as follows:
- No greater than 0.4 mg/dL (= 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%
- No prior chemotherapy, radiotherapy, or any antileukemic therapy
- Intrathecal cytarabine therapy given at diagnosis allowed
- Prior therapy for TMD allowed
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Minimum age
No limit
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Maximum age
4
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/03/2007
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
31/12/2021
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Sample size
Target
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Accrual to date
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Final
205
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
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Princess Margaret Hospital for Children - Perth
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Recruitment postcode(s) [1]
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6008 - Perth
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Recruitment outside Australia
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United States of America
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Arizona
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United States of America
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California
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United States of America
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Colorado
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United States of America
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Delaware
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United States of America
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Kentucky
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Louisiana
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Maine
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Vermont
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Wisconsin
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Ontario
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Santurce
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Funding & Sponsors
Primary sponsor type
Other
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Name
Children's Oncology Group
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Address
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Other collaborator category [1]
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Government body
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Name [1]
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National Cancer Institute (NCI)
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Ethics approval
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Summary
Brief summary
This phase III trial is studying how well combination chemotherapy works in treating young
patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. Drugs
used in chemotherapy work in different ways to stop the growth of cancer cells, either by
killing the cells or by stopping them from dividing. Giving more than one drug (combination
chemotherapy) may kill more cancer cells.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00369317
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Jeffrey Taub, MD
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Address
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Children's Oncology Group
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00369317
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