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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/NCT00003593




Registration number
NCT00003593
Ethics application status
Date submitted
1/11/1999
Date registered
27/01/2003
Date last updated
27/06/2013

Titles & IDs
Public title
Chemotherapy in Treating Children With Down Syndrome and Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome
Scientific title
Treatment of Children With Down Syndrome (DS) and Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Transient Myeloproliferative Disorder (TMD): A Phase III Group-Wide Study
Secondary ID [1] 0 0
COG-A2971
Secondary ID [2] 0 0
A2971
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Myelodysplastic Syndromes 0 0
Myelodysplastic/Myeloproliferative Neoplasms 0 0
Condition category
Condition code
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
Human Genetics and Inherited Disorders 0 0 0 0
Down's syndrome
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - asparaginase
Treatment: Drugs - cytarabine
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - methotrexate
Treatment: Drugs - therapeutic hydrocortisone
Treatment: Drugs - thioguanine

Experimental: Arm A: TMD patients only - Patients are observed if their transient myeloproliferative disorder (TMD) does not require intervention. Patients who require therapy for TMD undergo leukapheresis or exchange transfusion for up to 3 consecutive days. If the TMD does not resolve or there is significant organ involvement, patients receive low-dose cytarabine IV continuously on days 0-4. Treatment repeats at least every 2 weeks for up to 4 courses. Patients who experience a recurrence of TMD at least 8 weeks after resolution or have refractory disease may proceed to group II for further treatment. patients will continue to be followed for remission induction, EFS, DFS and OS regardless of the type of leukemia that develops.

Experimental: Arm B: AML/MDS patients only - (closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.


Treatment: Drugs: asparaginase
Given IV

Treatment: Drugs: cytarabine
Given IT

Treatment: Drugs: daunorubicin hydrochloride
Given IV

Treatment: Drugs: methotrexate
Given IV

Treatment: Drugs: therapeutic hydrocortisone
Given IT

Treatment: Drugs: thioguanine
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival
Timepoint [1] 0 0
Length of study

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Cytogenetically proven Down Syndrome (constitutional trisomy 21) with transient
myeloproliferative disorder (TMD), myelodysplastic syndromes (MDS), or acute
myelogenous leukemia (AML)

- Must be confirmed by bone marrow aspirate, cerebrospinal fluid exam, or blood
test

- Trisomy 21 mosaicism allowed

- Group I:

- Diagnosis of TMD in patients no older than 90 days at initial presentation

- Must have nonerythroid blasts (any amount) in the peripheral blood and one of the
following:

- Verification with a second sample

- More than 5% bone marrow blasts

- Hepatomegaly and/or splenomegaly

- Lymphadenopathy

- Cardiac or pleural effusions OR

- Histologically or cytologically proven TMD with blasts in an affected organ or in
fluid (pericardial, pleural, or peritoneal)

- Bone marrow aspirate is required

- Group II (closed to accrual as of 6/24/04):

- Diagnosis of MDS or AML (except M3 subtype) in patients older than 90 days with
more than 29% blasts in bone marrow (with or without history of TMD), or any of
the following histologies:

- Refractory anemia (RA)

- RA with excess blasts (RAEB)

- RAEB in transformation

- RA with ringed sideroblasts (RARS)

- Primary cytopenia (later confirmed by bone marrow aspirate as due to marrow
hypoplasia) defined by one or more of the following:

- Absolute neutrophil count less than 500/mm^3

- Untransfused platelet count less than 30,000/mm^3

- Untransfused hemoglobin less than 8 g/dL

- The following diagnoses will be observed only:

- RA with mild cytopenias*

- RARS with mild cytopenias*

- Mild primary cytopenias (one or more) without dysplasia (confirmed by hypoplastic
bone marrow exam) NOTE: * Platelet count 30-150,000/mm3, absolute neutrophil
count 500-1,499/mm3, and hemoglobin greater than 8 g/dL

- Granulocytic sarcoma (chloroma), with or without bone marrow involvement, allowed

PATIENT CHARACTERISTICS:

Age:

- See Disease Characteristics

- 21 and under

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- See Disease Characteristics

Renal:

- Not specified

Cardiovascular:

- Shortening fraction greater than 27% by echocardiogram* OR

- Ejection fraction greater than 47% by radionuclide angiogram* NOTE: *For patients with
MDS and AML (as of 2/24/04, previously diagnosed MDS or AML closed to accrual; MDS or
AML that develops (secondary to TMD) after study enrollment or MDS that requires
initial observation [with or without subsequent treatment] allowed)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Prior chemotherapy for TMD allowed

- No prior chemotherapy for malignancy

Endocrine therapy:

- Concurrent topical or inhaled steroids for other conditions allowed

Radiotherapy:

- No prior radiotherapy for malignancy

Surgery:

- Not specified

Other:

- No prior antileukemic therapy

- Prior enrollment on this study for TMD allowed
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
1/06/1999
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2012
Sample size
Target
Accrual to date
Final
254
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6001 - Perth
Recruitment outside Australia
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Alabama
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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
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating
children who have Down syndrome and myeloproliferative disorder, acute myelogenous leukemia,
or myelodysplastic syndrome.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00003593
Trial related presentations / publications
Perentesis JP, Alonzo TA, Gerbing R, et al.: Polymorphism in folate metabolism and outcomes of therapy in children with AML with and without Down Syndrome. [Abstract] Blood 102 (11 Pt 1): A-479, 2003.
Public notes

Contacts
Principal investigator
Name 0 0
Alan S. Gamis, MD, MPH
Address 0 0
Children's Mercy Hospital Kansas City
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00003593