ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

May 6, 2026 updated by: National Hospital Organization Nagoya Medical Center

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
    • New Territories
      • Shatin, New Territories, Hong Kong
        • Prince of Wales Hospital
  • Japan
      • Kagoshima, Japan, 890-8544
        • Kagoshima University Hospital
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University of Malaya Medical Centre
      • Subang Jaya, Malaysia, 47500
        • Subang Jaya Medical Centre
  • Singapore
      • Singapore, Singapore, 229899
        • KK Women's and Children's Hospital
      • Singapore, Singapore, 119074
        • National University Hospital
  • Taiwan
      • Taipei, Taiwan, 10449
        • Mackay Memorial Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Children's Hospital
      • Taoyuan, Taiwan, 333
        • Chang Gung Memorial Hopsital, Linkou
  • Thailand
      • Bangkok, Thailand, 10700
        • Siriraj Hospital Mahidol University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. 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.
    2. Ongoing uncontrolled hypertension.
    3. Ongoing uncontrolled diabetes mellitus.
    4. Ongoing uncontrolled infection.
    5. History of congenital or acquired immunodeficiency including HIV infection.
    6. History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severe pulmonary emphysema.
    7. CNS hemorrhage.
    8. Psychiatric disorder.
    9. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SR

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.
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cy
Drug: Vincristine
Given IV
Other Names:
  • VCR
Drug: Daunorubicin
Given IV
Other Names:
  • DNR
Drug: Prednisolone
Given PO or IV
Other Names:
  • Pred
Drug: Epirubicin
Given IV
Other Names:
  • EPI
Drug: E-coli L-asparaginase
Given IM or IV
Other Names:
  • E-coli L-Asp
Drug: 6-Mercaptopurine
Given PO
Other Names:
  • 6-MP
Drug: Methotrexate
Given IV, PO or IT
Other Names:
  • MTX
Drug: Hydrocortisone
Given IT
Drug: Cytarabine
Given IV, IT or SC
Other Names:
  • Ara-C
Experimental: LR

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.
Drug: Vincristine
Given IV
Other Names:
  • VCR
Drug: Daunorubicin
Given IV
Other Names:
  • DNR
Drug: Prednisolone
Given PO or IV
Other Names:
  • Pred
Drug: Epirubicin
Given IV
Other Names:
  • EPI
Drug: E-coli L-asparaginase
Given IM or IV
Other Names:
  • E-coli L-Asp
Drug: 6-Mercaptopurine
Given PO
Other Names:
  • 6-MP
Drug: Methotrexate
Given IV, PO or IT
Other Names:
  • MTX
Drug: Hydrocortisone
Given IT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event Free Survival
Time Frame: Up to 5 years
Percentage of patients who are event free at 5 years.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 5 years
Percentage of patients who survive at 5 years.
Up to 5 years
Disease free survival
Time Frame: Up to 5 years
Percentage of patients who are leukemia free at 5 years.
Up to 5 years
Induction failure
Time Frame: 5 weeks
Percentage of patients who had failed induction.
5 weeks
Complete remission rate
Time Frame: 5 weeks
Percentage of patients who had achieved complete remission at the end of induction.
5 weeks
Cumulative incidence of relapse
Time Frame: Up to 5 years
Up to 5 years
Incidence of treatment-related adverse events
Time Frame: Up to 10 years
Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.
Up to 10 years
Flow MRD at day 15
Time Frame: At day 15 of induction therapy
To assess the prognostic value flow MRD level during induction for DS-ALL.
At day 15 of induction therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Hospital Organization Nagoya Medical Center

Investigators

  • Principal Investigator: Allen Yeoh, MBBS, National University Hospital, Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 18, 2017

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2033

Study Registration Dates

First Submitted

August 9, 2017

First Submitted That Met QC Criteria

September 13, 2017

First Posted (Actual)

September 18, 2017

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASIA-DS-ALL-2016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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