Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia (HR ALL)

Treatment of Newly Diagnosed High Risk Pediatric Acute Lymphoblastic Leukemia-prospective, Nationwide, Multi-center Study

• Clinical and genetic factors consistent with High risk : Induction → Consolidation

  1. BM MRD < 0.01% : IM #1 → DI #1 → IM #2 → Maintenance
  2. BM MRD ≥ 0.01% : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance
  3. BM MRD ≥ 0.01% after Consolidation
  1. T cell ALL : Change to very high risk regimen

  2. Pre-B ALL : IM #1 → Intensification

     1. BM MRD < 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance

     2. BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen

        • Difference in the number of 'interim maintenance(IM)' and 'delayed intensification(DI)' is important for chemotherapies based on MRD.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: ALL, High risk

Detailed Description

• Clinical and genetic factors consistent with High risk : Induction → Consolidation

  1. BM MRD < 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → Maintenance
  2. BM MRD ≥ 0.01% after Induction, < 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → Maintenance
  3. BM MRD ≥ 0.01% after Consolidation
  1. T cell ALL : Change to very high risk regimen

  2. Pre-B ALL : IM #1 → Intensification

     1. BM MRD < 0.01% after IM #1 : DI #1 → IM #2 → DI #2 → Maintenance

     2. BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimen

        • T cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.

• Study Type: Interventional
• Enrollment (Estimated): 370
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jae Wook Lee, Ph.D; Phone Number: 82-2-2258-6192; Email: dashwood@catholic.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Hyungjin Kang, MD, PhD; Phone Number: 82-010-3685-5164; Email: kanghj@snu.ac.kr
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Hyery Kim, Ph.D; Phone Number: 82-2-3010-3373; Email: taban@hanmail.net
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Heeyoung Ju, MD, PhD; Phone Number: 82-02-3410-6957; Email: hyju320@gmail.com
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Seung min Hahn, MD; Phone Number: 82-02-2228-2050; Email: bluenile88@yuhs.ac
  • Seoul, Korea, Republic of, 02841
    • Not yet recruiting
    • Korea University Anam Hospital
    • Contact: Jun Eun Park, Professor; Phone Number: +82-10-9476-0932; Email: pedonco@korea.ac.kr
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul Saint Mary's Hospital
    • Contact: Jae Wook Lee, Professor; Phone Number: 82-010-3249-0496; Email: dashwood@catholic.ac.kr
  • Yangsan, Korea, Republic of, 50612
    • 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>

• Age: 1year~19years of age at diagnosis

• Patients who are newly diagnosed Pre-B ALL and meet one of the following criteria

  • High-risk group according to the National Cancer Institute (NCI)/Rome: Age greater than or equal to 10 years and less than 19 years at diagnosis, or white blood cell count greater than or equal to 50 x 10^9/L at diagnosis
  • If extra-bone marrow lesions are identified at the time of diagnosis, Central nervous system involvement (CNS3) or testicular involvement
  • High-risk gene variants:

KMT2A rearrangement intrachromosomal amplification of chromosome 21 (iAMP21)

● If subjects are under the age of 10 at the time of diagnosis and took steroids for more than 24 hours within two weeks before the diagnosis, the risk group will be determined by the presence of a whole blood test within three days before starting steroids. If a whole blood test is performed within three days before beginning steroids, the risk group will be assessed based on the white blood cell count in the test. If there is no whole blood test before starting steroids, subjects are classified as a high-risk group. If subjects are ten or older at diagnosis, pre-diagnosis steroid treatment will not affect the risk classification.

• Newly diagnosed T cell ALL

<Exclusion Criteria>

• Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
• Patients with Down syndrome
• potential of pregnancy or during pregnancy (patients of childbearing age need adequate contraception for the duration of the trial)
• Patients who have already received steroid treatment for newly diagnosed ALL specified in the above selection criteria or chemotherapies more than one intrathecal cytarabine treatment
• Participating in an interventional clinical trial other than this research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ALL, High risk with DI #2(Doxorubicin); Clinical and genetic factors consistent with High risk : Induction → ConsolidationBM MRD < 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → MaintenanceBM MRD ≥ 0.01% after Induction, < 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → MaintenanceBM MRD ≥ 0.01% after ConsolidationT cell ALL : Change to very high risk regimenPre-B ALL : IM #1 → IntensificationBM MRD < 0.01% after IM #1 : Continue with 'No. 2' of High risk regimen starting with DI #1BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimenT cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.

Drug: ALL, High risk; Intervention Description : Clinical and genetic factors consistent with High risk : Induction → ConsolidationBM MRD < 0.01% after both Induction and Consolidation : IM #1 → DI #1 → IM #2 → MaintenanceBM MRD ≥ 0.01% after Induction, < 0.01% after Consolidation : IM #1 → DI #1 → IM #2 → DI #2 → MaintenanceBM MRD ≥ 0.01% after ConsolidationT cell ALL : Change to very high risk regimenPre-B ALL : IM #1 → IntensificationBM MRD < 0.01% after IM #1 : Continue with 'No. 2' of High risk regimen starting with DI #1BM MRD ≥ 0.01% after IM #1 : Change to Very high risk regimenT cell ALL patients with M1 BM post-Consolidation will start IM #1. However, the patients will switch to Very high risk regimen at the next chemotherapy cycle once post-Consolidation MRD ≥ 0.01% has been reported.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	Event-free survival rate for 5 years from the date of registration	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time until defined by date of all-cause mortality from the date of 1st infusion	Up to 5 years
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

Collaborators and Investigators

• Sponsor: Jae Wook Lee
• Collaborators: Samsung Medical Center; Asan Medical Center; Seoul National University Hospital; Korea University Anam Hospital; Severance Hospital; Pusan National University Yangsan Hospital
• Investigators: Study Chair: Jae Wook Lee, Ph.D, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2024
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 14, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

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

More Information

Terms related to this study

• Keywords: NGS-MRD; HR ALL
• 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
• Other Study ID Numbers: 2023-3626-0001

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