Clinical trial NCT03286634: ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Down Syndrome
Acute Lymphoblastic Leukemia
Childhood Cancer
Lead sponsor: National Hospital Organization Nagoya Medical Center
Sponsor class: OTHER
First posted: 2017-09-18
Enrollment: 60
Sex: ALL
Minimum age (years): 0
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: risk stratification-directed chemotherapy
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Event Free Survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 5 years
measure: Disease free survival
timeFrame: Up to 5 years
measure: Induction failure
timeFrame: 5 weeks
measure: Complete remission rate
timeFrame: 5 weeks
measure: Cumulative incidence of relapse
timeFrame: Up to 5 years
measure: Incidence of treatment-related adverse events
timeFrame: Up to 10 years
measure: Flow MRD at day 15
timeFrame: At day 15 of induction therapy
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Subang Jaya
country: Malaysia
facility: Subang Jaya Medical Centre
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Children's Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hopsital, Linkou
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
Study officials:
affiliation: National University Hospital, Singapore
name: Allen Yeoh, MBBS
role: PRINCIPAL_INVESTIGATOR
References: