Clinical trial NCT06257394: Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea
Official title: Multi-center Clinical Trial for Optimal Treatment of Pediatric Very High-risk Acute Lymphoblastic Leukemia in Korea
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia, Pediatric
Keywords: VHR ALL
NGS-MRD
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Asan Medical Center
name: Samsung Medical Center
name: Severance Hospital
name: Pusan National University Yangsan Hospital
name: Seoul St. Mary's Hospital
First posted: 2024-02-14
Enrollment: 74
Sex: ALL
Minimum age (years): 1
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Very high-risk acute lymphoblastic leukemia

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

Eligibility criteria: 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 \&lt; 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

Primary outcomes:
measure: Event free survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 5 years
measure: Recurred rate
timeFrame: Up to 5 years
measure: Death rate related to infusion
timeFrame: Up to 5 years
measure: Adverse Event
timeFrame: From Day 1 of the clinical trial to 28 days after last drug administration
measure: The rate of Hematopoietic stem cell transplantation
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul saint Mary's Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
References: