Ma-Spore ALL 2020 Study
Phase 2
Recruiting
- Conditions
- B Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT06336395
- Lead Sponsor
- National University Hospital, Singapore
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
Inclusion Criteria
-
Has been diagnosed with B-lineage ALL as evidenced by:
- BMA blasts > 20% AND
- Leukemic process in the bone marrow, peripheral blood or any extra medullary tissue with confirmation of B-lymphoid differentiation by flow immunophenotyping or histopathologically
-
Age < 41 years of age at enrolment
-
Written informed consent obtained from patient or legally acceptable representative (LAR)
Exclusion Criteria
- T-lineage ALL
- Down syndrome with ALL
- History of previous malignancies or this ALL is a second malignancy
- Mixed phenotype acute leukemia (MPAL) or undifferentiated leukemia
- Mature B-cell leukemia/lymphoma
- 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.
- 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.
- Liver dysfunction with direct bilirubin > 10x upper normal limit for age.
- Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy
- Doubtful compliance or ability to complete study therapy due to financial, social, familial or geographic reason, or in the judgement of site investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High risk (HR) Erwinase Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Thioguanine Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT Standard risk (SR) Pegylated asparaginase 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Vincristine 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Dexamethasone 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Prednisolone 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 High risk (HR) Pegylated asparaginase Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Cyclophosphamide Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT Intermediate risk (IR) Rituximab Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Standard risk (SR) Cytarabine 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Intermediate risk (IR) Vincristine Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) L-Asparaginase Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Pegylated asparaginase Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions High risk (HR) Fludarabine Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT Standard risk (SR) Methotrexate 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) L-Asparaginase 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Erwinase 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Cyclophosphamide 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Standard risk (SR) Mercaptopurine 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Intermediate risk (IR) Prednisolone Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Standard risk (SR) Thioguanine 1. No anthracycline throughout the treatment. 2. CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4 Intermediate risk (IR) Dexamethasone Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Methotrexate Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Erwinase Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Cyclophosphamide Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Cytarabine Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Mercaptopurine Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Thioguanine Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions Intermediate risk (IR) Doxorubicin Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions High risk (HR) Prednisolone Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Dexamethasone Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Cytarabine Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Vincristine Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Methotrexate Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) L-Asparaginase Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Dasatinib Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Imatinib Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Mercaptopurine Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT High risk (HR) Doxorubicin Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (3)
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Subang Jaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
KK Women's and Children's Hospital
🇸🇬Singapore, Singapore