Ma-Spore ALL 2020 Study

Ma-Spore ALL-Seq 2020: RNA-Seq and IgH/TCR-Seq to Improve Risk Assignment in Childhood, Adolescent and Young Adult Acute Lymphoblastic Leukaemia

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.

Study Overview

• Status: Recruiting
• Conditions: B Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Prednisolone; Drug: Dexamethasone; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Thioguanine; Drug: Doxorubicin; Drug: Fludarabine; Drug: Methotrexate; Drug: L-Asparaginase; Drug: Pegylated asparaginase; Drug: Erwinase; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Rituximab; Drug: Dasatinib; Drug: Imatinib

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.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Allen Eng Juh Yeoh, MBBS; Phone Number: +65 67724406; Email: paeyej@nus.edu.sg

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
    • Contact: Hany Arrifin, MBBS; Phone Number: +603 79492065; Email: hany@ummc.edu.my
  • Kuala Lumpur, Malaysia, 47500
    • Recruiting
    • Subang Jaya Medical Centre
    • Sub-Investigator: Lee Lee Chan, MBBS
    • Contact: Hai Peng Lin; Phone Number: +603 56391621; Email: flslhp@gmail.com
• Singapore
  • Singapore, Singapore, 229899
    • Recruiting
    • KK Women's and Children's Hospital
    • Contact: Ah Moy Tan, MBBS; Phone Number: +65 63941039; Email: tan.ah.moy01@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard risk (SR); No anthracycline throughout the treatment.; 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; Oral; Drug: Dexamethasone; Oral; Drug: Vincristine; Intravenous; Drug: Cyclophosphamide; Intravenous; Drug: Thioguanine; Oral; Drug: Methotrexate; Oral/ intrathecal/intravenous/subcutaneous; Drug: L-Asparaginase; Intramuscular; Drug: Pegylated asparaginase; Intravenous; Drug: Erwinase; Optional for those allergic to E.coli/PEG L-asparaginase (intravenous); Drug: Cytarabine; Subcutaneous/ Intravenous; Drug: Mercaptopurine; Oral
Experimental: Intermediate risk (IR); 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; Oral; Drug: Dexamethasone; Oral; Drug: Vincristine; Intravenous; Drug: Cyclophosphamide; Intravenous; Drug: Thioguanine; Oral; Drug: Doxorubicin; Intravenous; Drug: Methotrexate; Oral/ intrathecal/intravenous/subcutaneous; Drug: L-Asparaginase; Intramuscular; Drug: Pegylated asparaginase; Intravenous; Drug: Erwinase; Optional for those allergic to E.coli/PEG L-asparaginase (intravenous); Drug: Cytarabine; Subcutaneous/ Intravenous; Drug: Mercaptopurine; Oral; Drug: Rituximab; Intravenous
Experimental: High risk (HR); Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT	Drug: Prednisolone; Oral; Drug: Dexamethasone; Oral; Drug: Vincristine; Intravenous; Drug: Cyclophosphamide; Intravenous; Drug: Thioguanine; Oral; Drug: Doxorubicin; Intravenous; Drug: Fludarabine; Intravenous; Drug: Methotrexate; Oral/ intrathecal/intravenous/subcutaneous; Drug: L-Asparaginase; Intramuscular; Drug: Pegylated asparaginase; Intravenous; Drug: Erwinase; Optional for those allergic to E.coli/PEG L-asparaginase (intravenous); Drug: Cytarabine; Subcutaneous/ Intravenous; Drug: Mercaptopurine; Oral; Drug: Dasatinib; Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral); Drug: Imatinib; Indicated only for ALL with BCR::ABL1 /BCR::ABL1-like/ tyrosine kinase fusion positive (oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival (EFS)	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	5 years from diagnosis

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Allen Eng Juh Yeoh, MBBS, professor

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Dexamethasone; Prednisolone; Cyclophosphamide; Rituximab; Doxorubicin; Fludarabine; Cytarabine; Methotrexate; Vincristine; Asparaginase; Mercaptopurine; Dasatinib; Thioguanine; Pegaspargase
• Other Study ID Numbers: 2019/00888

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No