ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
Down Syndrome, Acute Lymphoblastic Leukemia, Childhood Cancer
About this trial
This is an interventional treatment trial for Down Syndrome
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:
- 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.
Sites / Locations
- Prince of Wales HospitalRecruiting
- Kagoshima University HospitalRecruiting
- University of Malaya Medical Centre
- Subang Jaya Medical Centre
- National University HospitalRecruiting
- KK Women's and Children's HospitalRecruiting
- National Taiwan University Children's Hospital
- Mackay Memorial HospitalRecruiting
- Chang Gung Memorial Hopsital, Linkou
- Siriraj Hospital Mahidol UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
SR
LR
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.
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.