Down SyndromePhase 2NCT03286634
ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
A Phase 2 study testing Daunorubicin, Prednisolone and Vincristine in people with Down Syndrome and Acute Lymphoblastic Leukemia, run by National Hospital Organization Nagoya Medical Center at 10 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 to 20 years
- Conditions the study is for
- Down Syndrome, Acute Lymphoblastic Leukemia, Childhood Cancer
- What is being tested?
- Daunorubicin, Prednisolone and Vincristine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 10 sitesin 6 countries
- Study dates
- 18 Apr 2017to 31 Mar 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Psychiatric disorder.
- Other concurrent active neoplasms.
- Pregnant or lactating women.
- Doubtful compliance or ability to complete study therapy due to financial, social, familial or geographic reason, or in the judgement of site investigator.
Trial locations and contacts
10 sites in 6 countries.
10 sites in 6 countries
Taiwan3 sites
National Taiwan University Children's Hospital
Taipei, 100
Mackay Memorial Hospital
Taipei, 10449
Chang Gung Memorial Hopsital, Linkou
Taoyuan, 333
Malaysia2 sites
University of Malaya Medical Centre
Kuala Lumpur, 59100
Subang Jaya Medical Centre
Subang Jaya, 47500
Singapore2 sites
National University Hospital
Singapore, 119074
KK Women's and Children's Hospital
Singapore, 229899
About this study
Official title: 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
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.
- Being tested
- Daunorubicin, Prednisolone, Vincristine, Epirubicin, E-coli L-asparaginase
- Medical subject headings
- Down Syndrome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaunorubicinDrug
Also called DNR
Given IV
PrednisoloneDrug
Also called Pred
Given PO or IV
VincristineDrug
Also called VCR
Given IV
EpirubicinDrug
Also called EPI
Given IV
E-coli L-asparaginaseDrug
Also called E-coli L-Asp
Given IM or IV
6-MercaptopurineDrug
Also called 6-MP
Given PO
MethotrexateDrug
Also called MTX
Given IV, PO or IT
HydrocortisoneDrug
Given IT
CytarabineDrug
Also called Ara-C
Given IV, IT or SC
CyclophosphamideDrug
Also called Cy
Given IV
| Study group | Role | What they receive |
|---|---|---|
| SR | Experimental | Standard 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. Receives: Drug: Daunorubicin; Drug: Prednisolone; Drug: Vincristine; Drug: Epirubicin; Drug: E-coli L-asparaginase; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Hydrocortisone; Drug: Cytarabine; Drug: Cyclophosphamide |
| LR | Experimental | Low 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. Receives: Drug: Daunorubicin; Drug: Prednisolone; Drug: Vincristine; Drug: Epirubicin; Drug: E-coli L-asparaginase; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
Percentage of patients who are event free at 5 years.
Measured: Up to 5 years
Secondary outcomes (7)
Overall survival
Percentage of patients who survive at 5 years.
Measured: Up to 5 years
Disease free survival
Percentage of patients who are leukemia free at 5 years.
Measured: Up to 5 years
Induction failure
Percentage of patients who had failed induction.
Measured: 5 weeks
Complete remission rate
Percentage of patients who had achieved complete remission at the end of induction.
Measured: 5 weeks
Cumulative incidence of relapse
Measured: Up to 5 years
Incidence of treatment-related adverse events
Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.
Measured: Up to 10 years
Flow MRD at day 15
To assess the prognostic value flow MRD level during induction for DS-ALL.
Measured: At day 15 of induction therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2017
- Study start18 Apr 2017
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- risk stratification-directed chemotherapy
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Hospital Organization Nagoya Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allen Yeoh, MBBS, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03286634
- Sponsor's protocol ID
- ASIA-DS-ALL-2016
- Status last verified
- May 2026
- First submitted
- 9 Aug 2017
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03286634
- Acronym / sponsor ID
- ASIA-DS-ALL-2016
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Hospital Organization Nagoya Medical CenterUniversity, hospital or other
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2033 (estimated)
- First posted
- 18 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- risk stratification-directed chemotherapy
| Arm | Type | Receives |
|---|---|---|
| SR | Experimental | Drug: Daunorubicin, Drug: Prednisolone, Drug: Vincristine, Drug: Epirubicin, Drug: E-coli L-asparaginase, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Hydrocortisone, Drug: Cytarabine, Drug: CyclophosphamideStandard 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 | Experimental | Drug: Daunorubicin, Drug: Prednisolone, Drug: Vincristine, Drug: Epirubicin, Drug: E-coli L-asparaginase, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: HydrocortisoneLow 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. |
Who may qualify
- Ages
- 0 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaunorubicinAlso: DNRGiven IV | Drug | LR, SR |
| PrednisoloneAlso: PredGiven PO or IV | Drug | LR, SR |
| VincristineAlso: VCRGiven IV | Drug | LR, SR |
| EpirubicinAlso: EPIGiven IV | Drug | LR, SR |
| E-coli L-asparaginaseAlso: E-coli L-AspGiven IM or IV | Drug | LR, SR |
| 6-MercaptopurineAlso: 6-MPGiven PO | Drug | LR, SR |
| MethotrexateAlso: MTXGiven IV, PO or IT | Drug | LR, SR |
| HydrocortisoneGiven IT | Drug | LR, SR |
| CytarabineAlso: Ara-CGiven IV, IT or SC | Drug | SR |
| CyclophosphamideAlso: CyGiven IV | Drug | SR |
Primary outcome
Event Free Survival
Time frame: Up to 5 years
Percentage of patients who are event free at 5 years.
7 secondary outcomes
Overall survival
Time frame: Up to 5 years
Disease free survival
Time frame: Up to 5 years
Induction failure
Time frame: 5 weeks
Complete remission rate
Time frame: 5 weeks
Cumulative incidence of relapse
Time frame: Up to 5 years
Incidence of treatment-related adverse events
Time frame: Up to 10 years
Flow MRD at day 15
Time frame: At day 15 of induction therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allen Yeoh, MBBS principal investigator
National University Hospital, Singapore
10 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daunorubicin, Prednisolone and Vincristine in people with Down Syndrome and Acute Lymphoblastic Leukemia, run by National Hospital Organization Nagoya Medical Center at 10 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Taiwan, Malaysia, Singapore, Hong Kong, Japan and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.