Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea (VHR ALL)

Multi-center Clinical Trial for Optimal Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea

Very high-risk acute lymphoblastic leukemia

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, Pediatric
• Intervention / Treatment: Drug: Dasatinib(Sprycel) arm; Drug: Non-Dasatinib(Sprycel) arm

Detailed Description

• Arm A : Philadelphia chromosome-positive : Induction (Except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.)

  • Morphologic Complete Remission after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3

    1. If Minimal Residual Disease & qPCR not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine → DI(Delayed Intensification) #1 → IM(Interim Maintenance) #2 → DI(Delayed Intensification) #2 → Maintenance
    2. If Minimal Residual Disease or qPCR(Quantitative Polymerase Chain Reaction) positivie after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

  • M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

    1. If Minimal Residual Disease & qPCR(Quantitative Polymerase Chain Reaction) not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, HD Cytarabine

    2. If Minimal Residual Disease or qPCR(Quantitative Polymerase Chain Reaction) positivie after the post-reinduction : Consolidation #3 using Blinatumomab

       • In Arm A, except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.

• Arm B : Other VHR ALL except Philadelphia chromosome-positive : Induction

  • Morphologic Complete Remission after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3

    1. If Minimal Residual Disease not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)
    2. If Minimal Residual Disease positivie after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

  • M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCT(Hematopoietic Stem Cell Transplantation)

    1. If Minimal Residual Disease not detected after the post-consolidation #1 : Consolidation #3 using High Dose Methotrexate, High Dose Cytarabine
    2. If Minimal Residual Disease positivie after the post-reinduction : Consolidation #3 using Blinatumomab

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyoung Jin Kang, Ph.D; Phone Number: +82-2-2072-3452; Email: kanghj@snu.ac.kr
• Study Contact Backup: Name: Hyoung Jin Kang; Phone Number: +82220723452; Email: kanghj@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Hyoung Jin Kang, Professor; Phone Number: +82-2-2072-3452; Email: kanghj@snu.ac.kr
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Ho Joon Im, Professor; Phone Number: 8201062311573; Email: hojim@amc.seoul.kr
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Hee Young Ju, Professor; Phone Number: +82-2-3410-0865; Email: hyju320@gmail.com
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Seung-min Hahn, Professor; Phone Number: +82-2-2258-9943; Email: bluenile88@yuhs.ac
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul Saint Mary's Hospital
    • Contact: Jae Won Yoo, Professor; Phone Number: +82-2-2258-6763; Email: hoiring0209@gmail.com
  • Yangsan, Korea, Republic of, 50612
    • Not yet recruiting
    • Pusan National University Yangsan Hospital
    • Contact: Eu Jeen Yang, Professor; Phone Number: +82-10-6478-8489; Email: 41sirius@hanmail.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pediatric patients diagnosed with ALL between the ages of 1 and 19 years at the time of diagnosis who meet one or more of the following conditions:

  • Philadelphia chromosome-positive t(9;22)(q34;q11) or
  • Patients with failed remission who had blast > 5% on bone marrow test after initial remission induction therapy or
  • Hypodiploidy (Number of chromosomes < 44 (less than 44)) or
  • E2A-HLF(Hepatic Leukemia Factor) translocation-positive or
  • When the prognosis is judged to be poor according to NGS-MRD results among high-risk ALL patients (i) In B-ALL, the NGS-MRD(Next Generation Sequencing-Minimal Residual Disease) after consolidation therapy is 0.01% or more, and the NGS-MRD followed during interim maintenance treatment is also 0.01% or more, (ii) In T-ALL, NGS-MRD(Next Generation Sequencing-Minimal Residual Disease) is more than 0.01% after consolidation therapy

Exclusion Criteria:

• Participants with contraindications to medications
• When the study participant or their legal representative withdraws consent
• Pregnant or lactating women (patients of child-bearing potential require adequate contraception during the study period)
• Participants who are medically unsuitable to participate in this study at the discretion of the investigator Participants participating in other interventional studies other than this protocol

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [Arm A, Dasatinib(Sprycel) Arm]; ▪ Arm A : Philadelphia chromosome-positive : Induction (Except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.); Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3If MRD & qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → DI #1 → IM #2 → DI #2 → MaintenanceIf MRD or qPCR positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT; M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCTIf MRD & qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD CytarabineIf MRD or qPCR positive after the post-reinduction : Consolidation #3 using BlinatumomabIn Arm A, except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.	Drug: Dasatinib(Sprycel) arm; ▪ Arm A : Philadelphia chromosome-positive : Induction (Except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.); Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3If MRD & qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → DI #1 → IM #2 → DI #2 → MaintenanceIf MRD or qPCR positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT; M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCTIf MRD & qPCR not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD CytarabineIf MRD or qPCR positive after the post-reinduction : Consolidation #3 using BlinatumomabIn Arm A, except Consolidation #3 using Blinatumomab, all administration should be given with Dasatinib.
Experimental: [Arm B, Non-Dasatinib(Sprycel) Arm]; ▪ Arm B : Other VHR ALL except Philadelphia chromosome-positive : Induction; Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3If MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → Allogeneic HSCTIf MRD positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT; M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3 → Allogeneic HSCTIf MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD CytarabineIf MRD positive after the post-reinduction : Consolidation #3 using Blinatumomab	Drug: Non-Dasatinib(Sprycel) arm; ▪ Arm B : Other VHR ALL except Philadelphia chromosome-positive : Induction; Morphologic CR after the Induction : Consolidation #1 → Consolidation #2 → Consolidation #3If MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD Cytarabine → Allogeneic HSCTIf MRD positive after the post-consolidation #1 : Consolidation #3 using Blinatumomab →Allogeneic HSCT; M2 or M3 after the Induction : Re-induction → Consolidation #2 → Consolidation #3‡ → Allogeneic HSCTIf MRD not detected after the post-consolidation #1 : Consolidation #3 using HD MTX, HD CytarabineIf MRD positive after the post-reinduction : Consolidation #3 using Blinatumomab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event free survival	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurred rate	As the period from enrollment to disease progression/recurrence	Up to 5 years
Death rate related to infusion	The time until defined by date of drug-related mortality from the date of 1st infusion	Up to 5 years
Adverse Event		From Day 1 of the clinical trial to 28 days after last drug administration
Overall survival	The time until defined by date of all-cause mortality from the date of 1st infusion	Up to 5 years
The rate of Hematopoietic stem cell transplantation	The rate of Hematopoietic stem cell transplantation after the Induction and consolidation therapy	Up to 5 years

Collaborators and Investigators

• Sponsor: Hyoung Jin Kang
• Collaborators: Samsung Medical Center; Seoul St. Mary's Hospital; Asan Medical Center; Severance Hospital; Pusan National University Yangsan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2024
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: VHR ALL; NGS-MRD
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: H-2401-028-1500

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