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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02521493




Registration number
NCT02521493
Ethics application status
Date submitted
10/08/2015
Date registered
13/08/2015
Date last updated
7/11/2024

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 (EFS)
Timepoint [1] 0 0
Up to 2 years from study entry

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
4/07/2025
Actual
Sample size
Target
Accrual to date
Final
280
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
Country [12] 0 0
United States of America
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Hawaii
Country [13] 0 0
United States of America
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Idaho
Country [14] 0 0
United States of America
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Illinois
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Indiana
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Iowa
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Kentucky
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United States of America
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Louisiana
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Maine
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Maryland
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Massachusetts
Country [22] 0 0
United States of America
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Michigan
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Minnesota
Country [24] 0 0
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Mississippi
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Missouri
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Nevada
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New Hampshire
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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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United States of America
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North Dakota
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United States of America
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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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State/province [44] 0 0
Virginia
Country [45] 0 0
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State/province [45] 0 0
Washington
Country [46] 0 0
United States of America
State/province [46] 0 0
West Virginia
Country [47] 0 0
United States of America
State/province [47] 0 0
Wisconsin
Country [48] 0 0
Canada
State/province [48] 0 0
British Columbia
Country [49] 0 0
Canada
State/province [49] 0 0
Manitoba
Country [50] 0 0
Canada
State/province [50] 0 0
Nova Scotia
Country [51] 0 0
Canada
State/province [51] 0 0
Ontario
Country [52] 0 0
Canada
State/province [52] 0 0
Quebec
Country [53] 0 0
New Zealand
State/province [53] 0 0
Auckland
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New Zealand
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Christchurch
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Puerto Rico
State/province [55] 0 0
San Juan
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Saudi Arabia
State/province [56] 0 0
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02521493