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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/NCT02521493




Registration number
NCT02521493
Ethics application status
Date submitted
10/08/2015
Date registered
13/08/2015
Date last updated
24/11/2023

Titles & IDs
Public title
Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
Scientific title
Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome
Secondary ID [1] 0 0
NCI-2015-00324
Secondary ID [2] 0 0
AAML1531
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Down Syndrome 0 0
Myelodysplastic Syndrome 0 0
Myeloid Leukemia Associated With Down Syndrome 0 0
Myeloproliferative Neoplasm 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 - Asparaginase Erwinia chrysanthemi
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Etoposide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Mitoxantrone Hydrochloride
Treatment: Drugs - Thioguanine

Experimental: Arm A (standard risk) - INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days.
INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days.
INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days.
INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days.
(This arm is closed to accrual and treatment with amendment #4A 01/07/2019)

Experimental: Arm B (high risk) - INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days.
INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours and etoposide IV over 90-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days.
INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours Q12 hours on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi IM or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.


Treatment: Drugs: Asparaginase
Given IM or IV

Treatment: Drugs: Asparaginase Erwinia chrysanthemi
Given IM or IV

Treatment: Drugs: Cytarabine
Given IT and IV

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Mitoxantrone Hydrochloride
Given IV

Treatment: Drugs: Thioguanine
Given PO
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 probability at 2 years
Timepoint [1] 0 0
At 2 years

Eligibility
Key inclusion criteria
- Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism
(by karyotype or fluorescence in situ hybridization [FISH])

- Patient has one of the following:

- Patient has previously untreated de novo AML and meets the criteria for AML with
>= 20% bone marrow blasts as set out in the World Health Organization (WHO)
Myeloid Neoplasm classification

- Attempts to obtain bone marrow either by aspirate or biopsy must be made
unless clinically prohibitive; in cases where it is clinically prohibitive,
peripheral blood with an excess of 20% blasts and in which adequate flow
cytometric and cytogenetics/FISH testing is feasible can be substituted for
the marrow exam at diagnosis

- Patient has cytopenias and/or bone marrow blasts but does not meet the criteria
for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20%
marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome
(MDS)

- For patients who do not meet criteria for AML or MDS as outlined above; patient
has a history of transient myeloproliferative disorder (which may or may not have
required chemotherapy intervention and:

- Is > 8 weeks since resolution of transient myeloproliferative disease (TMD)
with >= 5% blasts, OR

- Has an increasing blast count (>= 5%) in serial bone marrow aspirates
performed at least 4 weeks apart

- Children who have previously received chemotherapy, radiation therapy or any
anti-leukemic therapy are not eligible for this protocol, with the exception of
cytarabine for the treatment of TMD

- There are no minimal organ function requirements for enrollment on this study

- Note: Previous cardiac repair with sufficient cardiac function is not an
exclusion criteria

- Each patient's parents or legal guardians must sign a written informed consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human subjects research must be met
Minimum age
91 Days
Maximum age
3 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with promyelocytic leukemia (French-American-British [FAB] M3)

- Prior therapy

- Patients =< 30 days from the last dose of cytarabine used for treatment of TMD

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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2024
Actual
Sample size
Target
312
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [6] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Alaska
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Georgia
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Idaho
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Illinois
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Indiana
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Kentucky
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Maine
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Massachusetts
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Michigan
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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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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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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San Juan
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Saudi Arabia
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Riyadh

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 studies response-based chemotherapy in treating newly diagnosed acute
myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs
used in chemotherapy work in different ways to stop the growth of cancer cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Response-based chemotherapy separates patients into different risk groups and treats them
according to how they respond to the first course of treatment (Induction I). Response-based
treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in
younger patients with Down syndrome while reducing the side effects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02521493
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason N Berman
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02521493