Ma-Spore ALL 2020 Study

National University Health System (NUHS)

Status and phase: Enrolling; Phase 2

Conditions: B Lymphoblastic Leukemia

Treatments: Drug: Cyclophosphamide; Drug: Pegylated asparaginase; Drug: Vincristine; Drug: Thioguanine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Prednisolone; Drug: Rituximab; Drug: Imatinib; Drug: Dasatinib; Drug: Cytarabine; Drug: Doxorubicin; Drug: Erwinase; Drug: Mercaptopurine; Drug: Fludarabine; Drug: L-Asparaginase

Study type: Interventional

Funder types: Other

Identifiers

NCT06336395

2019/00888

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 3 patient groups

Standard risk (SR)

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Vincristine

Drug: Pegylated asparaginase

Drug: Mercaptopurine

Drug: Cyclophosphamide

Drug: Thioguanine

Drug: Prednisolone

Drug: Cytarabine

Drug: Methotrexate

Drug: Erwinase

Drug: L-Asparaginase

Intermediate risk (IR)

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Vincristine

Drug: Pegylated asparaginase

Drug: Doxorubicin

Drug: Mercaptopurine

Drug: Cyclophosphamide

Drug: Thioguanine

Drug: Rituximab

Drug: Prednisolone

Drug: Cytarabine

Drug: Methotrexate

Drug: Erwinase

Drug: L-Asparaginase

High risk (HR)

Experimental group

Description:

Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT

Treatment:

Drug: Dasatinib

Drug: Dexamethasone

Drug: Vincristine

Drug: Fludarabine

Drug: Pegylated asparaginase

Drug: Doxorubicin

Drug: Mercaptopurine

Drug: Cyclophosphamide

Drug: Thioguanine

Drug: Imatinib

Drug: Prednisolone

Drug: Cytarabine

Drug: Methotrexate

Drug: Erwinase

Drug: L-Asparaginase