Malaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study

Ma-Spore ALL 2010 Study

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.

Study Overview

• Status: Unknown
• Conditions: Acute Lymphoblastic Leukemia (ALL)
• Intervention / Treatment: Drug: Prednisolone; Drug: Dexamethasone; Drug: L-Asparaginase; Drug: Vincristine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: 6-Mercaptopurine; Drug: Thioguanine; Drug: Doxorubicin; Drug: Daunorubicin; Drug: Fludarabine; Drug: Imatinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Allen Yeoh, MBBS; Phone Number: (+65) 6772 4406; Email: allen_yeoh@nuhs.edu.sg

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University of Malaya Medical Centre
    • Contact: Hany Arrifin, MBBS; Phone Number: +603 7949 6785; Email: hany@ummc.edu.my
  • Subang Jaya, Malaysia, 47500
    • Recruiting
    • Subang Jaya Medical Centre
    • Contact: Lee Lee Chan, MBBS; Email: drchanleelee@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
  • Singapore, Singapore, 119074
    • Recruiting
    • National University Hospital
    • Contact: Allen Yeoh, MBBS; Phone Number: (+65) 6772 4406; Email: allen_yeoh@nuhs.edu.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed diagnosis of non-Burkitt B-lineage ALL
2. 1 to 17 years of age (before 18th birthday)
3. Renal function within normal range for age
4. Liver function within normal range for age
5. Able to participate in the full 2 years of treatment

Exclusion Criteria:

1. Age less than one year or age greater than/equals to 18 years
2. Previous treatment with cytotoxic agents or high-dose steroids
3. Mixed phenotype acute leukemia (MPAL)
4. ALL as secondary malignancy
5. Abnormal renal or liver function
6. Doubtful compliance or unable to afford full course of therapy

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
Other: Standard Risk (SR)	Drug: Prednisolone; Oral; Drug: Dexamethasone; Oral; Drug: L-Asparaginase; Intramuscular injection; Drug: Vincristine; Intravenous; Drug: Methotrexate; Intrathecal/ Intravenous/ Oral; Drug: Cyclophosphamide; Intravenous; Drug: Cytarabine; Intravenous/ Subcutaneous injection; Drug: 6-Mercaptopurine; Oral; Drug: Thioguanine; Oral
Other: Intermediate Risk (IR)	Drug: Prednisolone; Oral; Drug: Dexamethasone; Oral; Drug: L-Asparaginase; Intramuscular injection; Drug: Vincristine; Intravenous; Drug: Methotrexate; Intrathecal/ Intravenous/ Oral; Drug: Cyclophosphamide; Intravenous; Drug: Cytarabine; Intravenous/ Subcutaneous injection; Drug: 6-Mercaptopurine; Oral; Drug: Thioguanine; Oral; Drug: Doxorubicin; Intravenous
Other: High risk (HR)	Drug: Prednisolone; Oral; Drug: Dexamethasone; Oral; Drug: L-Asparaginase; Intramuscular injection; Drug: Vincristine; Intravenous; Drug: Methotrexate; Intrathecal/ Intravenous/ Oral; Drug: Cyclophosphamide; Intravenous; Drug: Cytarabine; Intravenous/ Subcutaneous injection; Drug: 6-Mercaptopurine; Oral; Drug: Thioguanine; Oral; Drug: Doxorubicin; Intravenous; Drug: Daunorubicin; Intravenous; Drug: Fludarabine; Intravenous; Drug: Imatinib; Oral (For BCR-ABL ALL only)

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Allen Yeoh, MBBS, Ma-spore Group

Publications and helpful links

General Publications

• Yeoh AEJ, Lu Y, Chin WHN, Chiew EKH, Lim EH, Li Z, Kham SKY, Chan YH, Abdullah WA, Lin HP, Chan LL, Lam JCM, Tan PL, Quah TC, Tan AM, Ariffin H. Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study. J Clin Oncol. 2018 Sep 10;36(26):2726-2735. doi: 10.1200/JCO.2018.78.3050. Epub 2018 Jul 25.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: August 25, 2016
• First Submitted That Met QC Criteria: September 5, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Estimate): September 30, 2016
• Last Update Submitted That Met QC Criteria: September 29, 2016
• Last Verified: September 1, 2016

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; 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; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Prednisolone; Cyclophosphamide; Doxorubicin; Fludarabine; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine
• Other Study ID Numbers: Ma-Spore ALL 2010