Malaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study

Study Overview
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Brief Summary
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The overall objective of this study is to continue to improve the cure rate of childhood acute lymphoblastic leukemia (ALL) in Singapore and Malaysia in the context of a multi-centre cooperative trial using a risk-stratified therapy based primarily on early response to therapy utilizing a simplified minimal residual disease (MRD-lite) platform.

Detailed Description
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The study was designed on the premise that a risk classification strategy combining clinical and genetic presenting features with molecular assessment of MRD should reduce both treatment-related toxicities and relapse risk. The patient will be assigned to one of the 3 risk groups depending on his/her response to the treatment and special laboratory tests. There are no experimental drugs in this study. All the drugs used are standard established treatment for childhood ALL for the last 30 years. The difference in treatment is by changes in the frequency and dose of the chemotherapy drugs. The overall study treatment lasts for about 2 years.

Official Title
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Ma-Spore ALL 2010 Study

Conditions
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Acute Lymphoblastic Leukemia (ALL)

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Dexamethasone
* Drug: L-Asparaginase
* Drug: Vincristine
* Drug: Methotrexate
* Drug: Daunorubicin
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Cytarabine
* Drug: 6-Mercaptopurine
* Drug: Thioguanine
* Drug: Fludarabine
* Drug: Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of non-Burkitt B-lineage ALL 1 to 17 years of age (before 18th birthday) Renal function within normal range for age Liver function within normal range for age Able to participate in the full 2 years of treatment Exclusion Criteria: Age less than one year or age greater than/equals to 18 years Previous treatment with cytotoxic agents or high-dose steroids Mixed phenotype acute leukemia (MPAL) ALL as secondary malignancy Abnormal renal or liver function Doubtful compliance or unable to afford full course of therapy

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard Risk (SR)<br> | Drug: Prednisolone<br>* Oral<br>Drug: Dexamethasone<br>* Oral<br>Drug: L-Asparaginase<br>* Intramuscular injection<br>Drug: Vincristine<br>* Intravenous<br>Drug: Methotrexate<br>* Intrathecal/ Intravenous/ Oral<br>Drug: Cyclophosphamide<br>* Intravenous<br>Drug: Cytarabine<br>* Intravenous/ Subcutaneous injection<br>Drug: 6-Mercaptopurine<br>* Oral<br>Drug: Thioguanine<br>* Oral<br>|
| Other: Intermediate Risk (IR)<br> | Drug: Prednisolone<br>* Oral<br>Drug: Dexamethasone<br>* Oral<br>Drug: L-Asparaginase<br>* Intramuscular injection<br>Drug: Vincristine<br>* Intravenous<br>Drug: Methotrexate<br>* Intrathecal/ Intravenous/ Oral<br>Drug: Doxorubicin<br>* Intravenous<br>Drug: Cyclophosphamide<br>* Intravenous<br>Drug: Cytarabine<br>* Intravenous/ Subcutaneous injection<br>Drug: 6-Mercaptopurine<br>* Oral<br>Drug: Thioguanine<br>* Oral<br>|
| Other: High risk (HR)<br> | Drug: Prednisolone<br>* Oral<br>Drug: Dexamethasone<br>* Oral<br>Drug: L-Asparaginase<br>* Intramuscular injection<br>Drug: Vincristine<br>* Intravenous<br>Drug: Methotrexate<br>* Intrathecal/ Intravenous/ Oral<br>Drug: Daunorubicin<br>* Intravenous<br>Drug: Doxorubicin<br>* Intravenous<br>Drug: Cyclophosphamide<br>* Intravenous<br>Drug: Cytarabine<br>* Intravenous/ Subcutaneous injection<br>Drug: 6-Mercaptopurine<br>* Oral<br>Drug: Thioguanine<br>* Oral<br>Drug: Fludarabine<br>* Intravenous<br>Drug: Imatinib<br>* Oral (For BCR-ABL ALL only)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) | EFS was estimated from time of diagnosis to time of first event or of patient's last follow-up. Failure to achieve complete remission (CR), relapse, death in continuous remission from whatever cause, secondary leukemia and abandonment (absence from scheduled therapy for more than 6 weeks) were considered as events. | 5 years | 
| Overall survival (OS) | OS was determined from diagnosis to time of death from any cause. | 5 years | 
| Minimal residual disease (MRD) measurement |  | At time point of Day 33, week 8 and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with chemotherapy-related adverse events as assessed by CTCAE version 4.0 |  | Through study completion, an average of 2 years | 
| Dose intensity of chemotherapy during various phases of therapy |  | Through study completion, an average of 2 years |