ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
Asia-wide, Multicenter Open-label, Phase II Non-randomised Study Involving Children With Down Syndrome Under 21 Year-old With Newly Diagnosed, Treatment naïve Acute Lymphoblastic Leukemia
1 other identifier
interventional
60
6 countries
10
Brief Summary
To evaluate the outcome of a prednisolone and low dose methotrexate based protocol in Down syndrome children with ALL (DS-ALL) in an Asia-wide study. The treatment protocol was modified based upon backbone of Taiwan Pediatric Oncology Group (TPOG)-ALL protocol in which risk classification will be guided by level of flow minimal residual disease (MRD) instead.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2017
Longer than P75 for phase_2
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 18, 2017
CompletedFirst Submitted
Initial submission to the registry
August 9, 2017
CompletedFirst Posted
Study publicly available on registry
September 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2033
September 28, 2022
September 1, 2022
11 years
August 9, 2017
September 26, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Event Free Survival
Percentage of patients who are event free at 5 years.
Up to 5 years
Secondary Outcomes (7)
Overall survival
Up to 5 years
Disease free survival
Up to 5 years
Induction failure
5 weeks
Complete remission rate
5 weeks
Cumulative incidence of relapse
Up to 5 years
- +2 more secondary outcomes
Study Arms (2)
SR
EXPERIMENTALStandard Risk (SR) : CNS 3 or CNS 2 regardless of response OR Time-point #1 (Day 15 induction) Flow MRD ≥ 1% (treatment will not be de-escalated even MRD \<0.01% by TP#2) OR Time-point #2 (Day 1 IDMTX/MP of Consolidation) ≥0.01% SR strategy: All SR patient will have to receive two doses of anthracycline and 12 L-asparaginase doses during induction except those who are escalated to SR at time point 2 when MRD ≥0.01%. During the first year of maintenance phase (48 weeks; 4x12 weeks blocks), cyclophosphamide and cytarabine bolus will be administered at 4 weekly interval.
LR
EXPERIMENTALLow Risk (LR): Time-point #1 (Day 15 induction) Flow MRD \<1% AND Time-point #2 (Day 1 IDMTX/MP of Consolidation) \<0.01% AND CNS 1 only LR strategy: For LR patients, one dose of anthracycline and 3 doses of L-asparaginase will be omitted during induction. Following re-induction I, interim maintenance and additional block of re-induction ie. re-induction II prior to maintenance phase will be omitted for LR patients.
Interventions
Eligibility Criteria
You may qualify if:
- Down syndrome diagnosed clinically or cytogenetically (including Mosaic Down)
- Newly diagnosed ALL according to WHO 2016 classification.
- Age \< 21 years old at time of enrollment.
- ECOG performance status (PS) score of 0-2.
- Written informed consent obtained from legally acceptable representatives.
You may not qualify if:
- Second malignancy.
- Philadelphia positive ALL.
- Mature B-ALL.
- Mixed phenotype acute leukemia.
- Any previous treatment with cytotoxic chemotherapy excluding treatment for TAM or radiation therapy. Patient pre-treated with short term steroid (\< 7 days of duration within last 1 month prior to treatment start) can be enrolled into this study.
- Renal dysfunction with creatinine \>2x upper limit of normal (ULN). Patients whose creatinine has improved to \<2x ULN before treatment commencement can enrol subject to discretion of site PI.
- Liver dysfunction with direct bilirubin \> 5x ULN.
- Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy, including:
- History of coronary arterial disease, cardiomyopathy, heart failure, arrhythmia (other than sinus arrhythmia) or severe cardiac malformation which with residual abnormalities or requires further major corrective surgery within 2 years.
- Ongoing uncontrolled hypertension.
- Ongoing uncontrolled diabetes mellitus.
- Ongoing uncontrolled infection.
- History of congenital or acquired immunodeficiency including HIV infection.
- History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severe pulmonary emphysema.
- CNS hemorrhage.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Prince of Wales Hospital
Shatin, New Territories, Hong Kong
Kagoshima University Hospital
Kagoshima, 890-8544, Japan
University of Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Subang Jaya Medical Centre
Subang Jaya, 47500, Malaysia
National University Hospital
Singapore, 119074, Singapore
KK Women's and Children's Hospital
Singapore, 229899, Singapore
National Taiwan University Children's Hospital
Taipei, 100, Taiwan
Mackay Memorial Hospital
Taipei, 10449, Taiwan
Chang Gung Memorial Hopsital, Linkou
Taoyuan District, 333, Taiwan
Siriraj Hospital Mahidol University
Bangkok, 10700, Thailand
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Allen Yeoh, MBBS
National University Hospital, Singapore
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 9, 2017
First Posted
September 18, 2017
Study Start
April 18, 2017
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2033
Last Updated
September 28, 2022
Record last verified: 2022-09