ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03286634
• Other study ID #: ASIA-DS-ALL-2016
• Status: Recruiting
• Phase: Phase 2
• Start date: April 18, 2017
• Est. completion date: March 31, 2033

Study information

• Verified date: September 2022
• Source: National Hospital Organization Nagoya Medical Center
• Contact: Allen Yeoh, MBBS
• Phone: (65) 67724406
• Email: paeyej[@]nus.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 flow minimal residual disease (MRD) instead.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 31, 2033
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 20 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Childhood Cancer
• Down Syndrome
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Syndrome

Intervention

Drug:
• Daunorubicin
Given IV
• Prednisolone
Given PO or IV
• Vincristine
Given IV
• Epirubicin
Given IV
• E-coli L-asparaginase
Given IM or IV
• 6-Mercaptopurine
Given PO
• Methotrexate
Given IV, PO or IT
• Hydrocortisone
Given IT
• Cytarabine
Given IV, IT or SC
• Cyclophosphamide
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Hospital Organization Nagoya Medical Center

Countries where clinical trial is conducted

Hong Kong,  Japan,  Malaysia,  Singapore,  Taiwan,  Thailand, 

Outcome

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