Ma-Spore ALL 2020 Study

NCT06336395 | Recruiting Phase 2 DMC

• 1 other identifier: 2019/00888
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 3

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.

Conditions

B Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  OS is calculated from the date of diagnosis to the date of last follow-up or any death

  5 years from diagnosis

Secondary Outcomes (1)

• Event free survival (EFS)

  5 years from diagnosis

Other Outcomes (2)

• 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

Study Arms (3)

Standard risk (SR)

EXPERIMENTAL

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

Drug: Prednisolone; Drug: Dexamethasone; Drug: Vincristine; Drug: Methotrexate; Drug: L-Asparaginase; Drug: Pegylated asparaginase; Drug: Erwinase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Thioguanine

Intermediate risk (IR)

EXPERIMENTAL

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

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

High risk (HR)

EXPERIMENTAL

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

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

Interventions

Prednisolone DRUG

Oral

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Dexamethasone DRUG

Oral

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Vincristine DRUG

Intravenous

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Methotrexate DRUG

Oral/ intrathecal/intravenous/subcutaneous

High risk (HR); Intermediate risk (IR); Standard risk (SR)

L-Asparaginase DRUG

Intramuscular

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Pegylated asparaginase DRUG

Intravenous

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Erwinase DRUG

Optional for those allergic to E.coli/PEG L-asparaginase (intravenous)

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Dasatinib DRUG

Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral)

High risk (HR)

Imatinib DRUG

Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral)

High risk (HR)

Cyclophosphamide DRUG

Intravenous

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Cytarabine DRUG

Subcutaneous/ Intravenous

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Mercaptopurine DRUG

Oral

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Thioguanine DRUG

Oral

High risk (HR); Intermediate risk (IR); Standard risk (SR)

Rituximab DRUG

Intravenous

Intermediate risk (IR)

Doxorubicin DRUG

Intravenous

High risk (HR); Intermediate risk (IR)

Fludarabine DRUG

Intravenous

High risk (HR)

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (3)

Subang Jaya Medical Centre

Kuala Lumpur, 47500, Malaysia

RECRUITING

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

RECRUITING

KK Women's and Children's Hospital

Singapore, 229899, Singapore

RECRUITING

MeSH Terms

Interventions

Prednisolone; Dexamethasone; Vincristine; Methotrexate; Asparaginase; pegaspargase; Dasatinib; Imatinib Mesylate; Cyclophosphamide; Cytarabine; Mercaptopurine; Thioguanine; Rituximab; Doxorubicin; fludarabine

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Purines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Allen Eng Juh Yeoh, MBBS

  Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Allen Eng Juh Yeoh, MBBS

CONTACT

+65 67724406; paeyej@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 28, 2024
• Study Start: March 4, 2020
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 28, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

MY (2); SG (1)