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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00369317




Registration number
NCT00369317
Ethics application status
Date submitted
24/08/2006
Date registered
29/08/2006
Date last updated
14/08/2017

Titles & IDs
Public title
Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
Scientific title
The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years
Secondary ID [1] 0 0
NCI-2009-00318
Secondary ID [2] 0 0
AAML0431
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Acute Basophilic Leukemia 0 0
Childhood Acute Eosinophilic Leukemia 0 0
Childhood Acute Erythroleukemia (M6) 0 0
Childhood Acute Megakaryocytic Leukemia (M7) 0 0
Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) 0 0
Childhood Acute Monoblastic Leukemia (M5a) 0 0
Childhood Acute Monocytic Leukemia (M5b) 0 0
Childhood Acute Myeloblastic Leukemia With Maturation (M2) 0 0
Childhood Acute Myeloblastic Leukemia Without Maturation (M1) 0 0
Childhood Acute Myelomonocytic Leukemia (M4) 0 0
Childhood Myelodysplastic Syndromes 0 0
de Novo Myelodysplastic Syndromes 0 0
Secondary Acute Myeloid Leukemia 0 0
Secondary Myelodysplastic Syndromes 0 0
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Human Genetics and Inherited Disorders 0 0 0 0
Down's syndrome

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS) at 3 Years
Timepoint [1] 0 0
Time from study entry to induction failure, relapse, or death assessed at 3 years.
Primary outcome [2] 0 0
Overall Survival (OS) at 3 Years
Timepoint [2] 0 0
Time from study entry to death, assessed at 3 years.
Secondary outcome [1] 0 0
Induction Remission Rate - Proportion of participants with a remission after four courses of Induction therapy.
Timepoint [1] 0 0
End of induction therapy (day 112)
Secondary outcome [2] 0 0
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 - Proportion of participants with at least one grade 3 or higher adverse event during therapy.
Timepoint [2] 0 0
From the beginning of induction therapy to the end of intensification therapy
Secondary outcome [3] 0 0
Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry - Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available.
Timepoint [3] 0 0
At the start of therapy
Secondary outcome [4] 0 0
Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis - Proportion of participants having GATA1 mutation among patients with phenotype data available.
Timepoint [4] 0 0
At baseline and at the end of therapy (intensification) or disease relapse
Secondary outcome [5] 0 0
Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry - Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment.
Timepoint [5] 0 0
After Induction I therapy (day 28 from start of therapy)
Secondary outcome [6] 0 0
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program - 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.
Timepoint [6] 0 0
Days 1, 2, 8, and 9 of induction II
Secondary outcome [7] 0 0
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program - 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.
Timepoint [7] 0 0
Days 1, 2, 8, and 9 of induction II
Secondary outcome [8] 0 0
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program - 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.
Timepoint [8] 0 0
Days 1, 2, 8, and 9 of induction II
Secondary outcome [9] 0 0
Gene Expression Profiles by Microarrays - 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.
Timepoint [9] 0 0
At baseline and at the time of relapse (if available)

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
Minimum age
No limit
Maximum age
4 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Idaho
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maine
Country [15] 0 0
United States of America
State/province [15] 0 0
Maryland
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Minnesota
Country [18] 0 0
United States of America
State/province [18] 0 0
Mississippi
Country [19] 0 0
United States of America
State/province [19] 0 0
Missouri
Country [20] 0 0
United States of America
State/province [20] 0 0
Nebraska
Country [21] 0 0
United States of America
State/province [21] 0 0
Nevada
Country [22] 0 0
United States of America
State/province [22] 0 0
New Jersey
Country [23] 0 0
United States of America
State/province [23] 0 0
New York
Country [24] 0 0
United States of America
State/province [24] 0 0
North Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
North Dakota
Country [26] 0 0
United States of America
State/province [26] 0 0
Ohio
Country [27] 0 0
United States of America
State/province [27] 0 0
Oklahoma
Country [28] 0 0
United States of America
State/province [28] 0 0
Oregon
Country [29] 0 0
United States of America
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Pennsylvania
Country [30] 0 0
United States of America
State/province [30] 0 0
Rhode Island
Country [31] 0 0
United States of America
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South Carolina
Country [32] 0 0
United States of America
State/province [32] 0 0
Tennessee
Country [33] 0 0
United States of America
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Texas
Country [34] 0 0
United States of America
State/province [34] 0 0
Utah
Country [35] 0 0
United States of America
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Vermont
Country [36] 0 0
United States of America
State/province [36] 0 0
Virginia
Country [37] 0 0
United States of America
State/province [37] 0 0
Washington
Country [38] 0 0
United States of America
State/province [38] 0 0
Wisconsin
Country [39] 0 0
Canada
State/province [39] 0 0
British Columbia
Country [40] 0 0
Canada
State/province [40] 0 0
Manitoba
Country [41] 0 0
Canada
State/province [41] 0 0
Newfoundland and Labrador
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Puerto Rico
State/province [43] 0 0
Santurce

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT00369317
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeffrey Taub, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications