Acute Lymphoblastic Leukemia, Childhood Cancer, Down Syndrome
Conditions
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.
Interventions
DRUGDaunorubicin
Given IV
DRUGPrednisolone
Given PO or IV
DRUGVincristine
Given IV
DRUGEpirubicin
Given IV
DRUGE-coli L-asparaginase
Given IM or IV
DRUG6-Mercaptopurine
Given PO
DRUGMethotrexate
Given IV, PO or IT
DRUGHydrocortisone
Given IT
DRUGCytarabine
Given IV, IT or SC
DRUGCyclophosphamide
Given IV
Sponsors
National Hospital Organization Nagoya Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
risk stratification-directed chemotherapy
Eligibility
Sex/Gender
ALL
Age
0 Years to 20 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival | Up to 5 years | Percentage of patients who are event free at 5 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 5 years | Percentage of patients who survive at 5 years. |
| Disease free survival | Up to 5 years | Percentage of patients who are leukemia free at 5 years. |
| Induction failure | 5 weeks | Percentage of patients who had failed induction. |
| Complete remission rate | 5 weeks | Percentage of patients who had achieved complete remission at the end of induction. |
| Cumulative incidence of relapse | Up to 5 years | — |
| Incidence of treatment-related adverse events | Up to 10 years | Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms. |
| Flow MRD at day 15 | At day 15 of induction therapy | To assess the prognostic value flow MRD level during induction for DS-ALL. |
Countries
Hong Kong, Japan, Malaysia, Singapore, Taiwan, Thailand
Contacts
PRINCIPAL_INVESTIGATORAllen Yeoh, MBBS
National University Hospital, Singapore
Outcome results
None listed