B Lymphoblastic Leukemia
Conditions
Brief summary
The primary objective of this trial is to improve the overall survival rate of children and young adult with B-lineage acute lymphoblastic leukemia (B-ALL) in Singapore and Malaysia in the context of a multicenter cooperative trial using a risk-stratified therapy.
Detailed description
This is a multicenter open-label phase II study involving children and young adult (\< 41 years old) who are newly diagnosed with B-ALL and treatment naïve. There will be 3 parallel cohorts whose risk to be stratified based upon leukemia genetics profiles and patient's treatment response: 1. Standard Risk (SR) 2. Intermediate Risk (IR) 3. High Risk (HR) All drugs being used are commercially available chemotherapy drugs. There will be no novel chemotherapeutic agent without marketing authorization being tested in this trial.
Interventions
DRUGPrednisolone
Oral
DRUGDexamethasone
Oral
DRUGVincristine
Intravenous
DRUGMethotrexate
Oral/ intrathecal/intravenous/subcutaneous
DRUGL-Asparaginase
Intramuscular
Intravenous
DRUGErwinase
Optional for those allergic to E.coli/PEG L-asparaginase (intravenous)
DRUGDasatinib
Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral)
DRUGImatinib
Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral)
DRUGCyclophosphamide
Intravenous
DRUGCytarabine
Subcutaneous/ Intravenous
DRUGMercaptopurine
Oral
DRUGThioguanine
Oral
DRUGRituximab
Intravenous
DRUGDoxorubicin
Intravenous
DRUGFludarabine
Intravenous
Sponsors
National University Hospital, Singapore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 40 Years
Healthy volunteers
No
Inclusion criteria
1. Has been diagnosed with B-lineage ALL as evidenced by: 1. BMA blasts \> 20% AND 2. Leukemic process in the bone marrow, peripheral blood or any extra medullary tissue with confirmation of B-lymphoid differentiation by flow immunophenotyping or histopathologically 2. Age \< 41 years of age at enrolment 3. Written informed consent obtained from patient or legally acceptable representative (LAR)
Exclusion criteria
1. T-lineage ALL 2. Down syndrome with ALL 3. History of previous malignancies or this ALL is a second malignancy 4. Mixed phenotype acute leukemia (MPAL) or undifferentiated leukemia 5. Mature B-cell leukemia/lymphoma 6. Any previous cytotoxic therapy (chemotherapy/radiotherapy/immunotherapy). Patient pre-treated with short term steroid (\< 7 days of duration within last 1 month prior to ALL treatment start) may be enrolled after discussion and written approval from PI. These patients should be treated on at least intermediate arm. 7. Persistent renal dysfunction with creatinine more than upper limit of normal for age before start of induction therapy. Patients requiring temporary dialysis without persistent renal dysfunction can qualify. 8. Liver dysfunction with direct bilirubin \> 10x upper normal limit for age. 9. Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy 10. 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 |
|---|---|---|
| Overall survival (OS) | 5 years from diagnosis | OS is calculated from the date of diagnosis to the date of last follow-up or any death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival (EFS) | 5 years from diagnosis | EFS will be calculated from the date of diagnosis of ALL to date of last follow-up or to the first event, including relapse, resistant disease, second malignancy and death |
Other
| Measure | Time frame |
|---|---|
| Cumulative incidence (CI) of relapse for all treated cohorts | 5 years from diagnosis |
| Cumulative incidence (CI) of therapy-related mortality (TRM) for all treated subjects | 5 years from diagnosis |
Countries
Malaysia, Singapore
Contacts
Primary ContactAllen Eng Juh Yeoh, MBBS
Outcome results
None listed