Treatment for Down Syndrome children with Acute Lymphoblastic Leukemia

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

This study is testing a new treatment plan using prednisolone and low-dose methotrexate for children with Down syndrome who have Acute Lymphoblastic Leukemia to see if it helps them do better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 0 Years to 20 Years
• Sex: All
• Sponsor: National Hospital Organization Nagoya Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation, methotrexate
• Locations: 10 sites (Shatin, New Territories and 9 other locations)
• Trial ID: NCT03286634 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of a treatment protocol using prednisolone and low-dose methotrexate for children with Down syndrome diagnosed with Acute Lymphoblastic Leukemia (ALL). The protocol is based on the Taiwan Pediatric Oncology Group's ALL guidelines, with risk classification determined by minimal residual disease levels. The study aims to gather data across multiple sites in Asia to assess outcomes and improve treatment strategies for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include children under 21 years old with a clinical or cytogenetic diagnosis of Down syndrome and newly diagnosed ALL.

Not a fit: Patients with second malignancies, Philadelphia positive ALL, or significant renal or liver dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment outcomes for children with Down syndrome and ALL.

How similar studies have performed: Other studies have shown promise in treating ALL in children, but this specific approach for Down syndrome patients is relatively novel.

Eligibility criteria

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.

Where this trial is running

Shatin, New Territories and 9 other locations

• Prince of Wales Hospital — Shatin, New Territories, Hong Kong (Recruiting)
• Kagoshima University Hospital — Kagoshima, Japan (Recruiting)
• University of Malaya Medical Centre — Kuala Lumpur, Malaysia (Not_yet_recruiting)
• Subang Jaya Medical Centre — Subang Jaya, Malaysia (Not_yet_recruiting)
• National University Hospital — Singapore, Singapore (Recruiting)
• KK Women's and Children's Hospital — Singapore, Singapore (Recruiting)
• National Taiwan University Children's Hospital — Taipei, Taiwan (Not_yet_recruiting)
• Mackay Memorial Hospital — Taipei, Taiwan (Recruiting)
• Chang Gung Memorial Hopsital, Linkou — Taoyuan, Taiwan (Not_yet_recruiting)
• Siriraj Hospital Mahidol University — Bangkok, Thailand (Recruiting)

Study contacts

• Principal investigator: Allen Yeoh, MBBS — National University Hospital, Singapore
• Study coordinator: Allen Yeoh, MBBS

Conditions Down Syndrome; Acute Lymphoblastic Leukemia; Childhood Cancer