Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia

Phase 2

Recruiting

• Conditions: Acute Lymphoid Leukemia
• Interventions: Drug: Reinduction(4weeks); Drug: Cosolodation 1st(3weeks); Drug: Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks; Drug: Consolidation 2nd(3weeks); Drug: Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks; Drug: Intensification course; Drug: Blinatumomab 1st(High Risk Group)_4 Weeks; Drug: Maintenance(12 Weeks/Cycle); Drug: Blinatumomab 2nd (High Risk Group)_4 Weeks; Procedure: Stem Cell Transplantation

• Registration Number: NCT05827549
• Lead Sponsor: Ho Joon Im

Brief Summary

This study is open-label, multi-center, prospective study, which targets childhood patients with relapsed acute lymphostatic leukemia including bone marrow recurrence. Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for relapsed acute lymphoblastic leukemia in children and adolescents.

Detailed Description

The Risk Assessment is classified as follows based on the NGS-MRD results evaluated after EOI(End of Induction).

\<Standard Risk\>

* Late (Relapse ≥ 1 year after off treatment) B-ALL marrow or Combined relapse AND

* End of induction MRD \< 0.01%

\<High Risk\>

* T-ALL marrow or combined relapse (any timing)

* All other B-ALL marrow or combined relapse cases

\<Very High Risk\>

• End of Induction BM ≥ M2 AND B -ALL marrow or combined relapse

Study Timeline

• Study First Submitted: 2023-03-16
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-25
• Study Start: 2024-04-04
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-04
• Last Update Posted: 2025-06-06
• Primary Completion: 2032-12-31
• Study Completion: 2032-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Patients <= 1 year and >22 years of age at the time of relapse will be eligible

• Participants must have a histologic diagnosis of acute lymphoblastic leukemia:

  • B-ALL: Precursor B-cell acute lymphoblastic leukemia
  • T-ALL: Precursor T-cell acute lymphoblastic leukemia

• 1st recurred acute lymphoblastic leukemia patients, recurred parts including marrow. Enrolling patients with combined extra medullary relapse including bone marrow is acceptable. (No limits for extra medullary site) Additionally, subjects whose blast cells in bone marrow are less than 5% (ALL whether type M2 or M3 must be definite)

• Patients who have never received allogeneic stem cell transplant

• Patients who have never received blinatumomab before

• Adequate Renal Function

  -A serum creatinine based on age/gender as follows:

  1 to &lt; 2 years - Male (0.6) Female (0.6) 2 to &lt; 6 years - Male (0.8) Female (0.8) 6 to &lt; 10 years - Male (1) Female (1) 10 to &lt; 13 years - Male (1.2) Female (1.2) 13 to &lt; 16 years - Male (1.5) Female (1.4)

  ≥ 16 years - Male (1.7) Female (1.4)

• Adequate Liver Function defined as a direct bilirubin &lt;3.0 mg/dL

• Adequate Cardiac Function defined as: Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by echocardiogram

• Lansky (age &lt; 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60% at screening

• Patients with a life expectancy of 1 or more year

• Patients who are expected to comply with all required study procedures and follow the study protocol in the opinion of the investigator

• Signed written informed consent and assent forms must be obtained prior to any study procedures

Exclusion Criteria

• Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
• Patients with Philadelphia chromosome positive (Ph+) ALL
• Patients with CD19-negative recurrent progenitor B-cell acute lymphoblastic leukemia (non-expression of CD19 in peripheral blood or bone marrow by flow cytometry) are not eligible for administration of Blinatumomab
• In case of relapsed within 1 month after the end of induction with the same 4-drug therapy used in this study
• Patients with mixed phenotype leukemia
• patient who was relapsed within 1 month after the end of induction therapy with the same 4-drug regimen to be used in this study.
• Patients with genetic syndrome: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome bone marrow failure syndrome
• Patients with known HIV
• Female patients who are not proved as infertile or pregnant (Evidence of infertility: History taking of possibilities of pregnancy or urine human chorionic gonadotrophin test negative, amenorrhea more than a year, Natural or artificial (Ex.hormone therapy) menopause status more than a year, surgical sterilization(Ex.Hysterectomy or ovariotomy etc)
• Currently receiving treatment in another investigational drug study or clinical trial
• Evidence of unstable conditions that would pose a risk to subject safety or interfere with the patients&#39; compliance
• Patients with clinically relevant central nervous system (CNS) pathology or active CNS involvement including: unstable epilepsy, uncontrolled seizure, paralysis, aphasia, history of severe brain injury, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder
• Known hypersensitivity to drugs or components to be administered: Idarubicin, Etoposide, Ifosfamide, Cytarabine, Vincristine, Mercaptopurine, Blinatumomab

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Risk group with B-ALL	Reinduction(4weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance
Standard Risk group with B-ALL	Cosolodation 1st(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance
Standard Risk group with B-ALL	Consolidation 2nd(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance
Standard Risk group with B-ALL	Intensification course	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance
Standard Risk group with B-ALL	Maintenance(12 Weeks/Cycle)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance
High Risk group with B-ALL	Reinduction(4weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
High Risk group with B-ALL	Cosolodation 1st(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
High Risk group with B-ALL	Consolidation 2nd(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
High Risk group with B-ALL	Blinatumomab 1st(High Risk Group)_4 Weeks	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
High Risk group with B-ALL	Blinatumomab 2nd (High Risk Group)_4 Weeks	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
High Risk group with B-ALL	Stem Cell Transplantation	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT
Very high Risk with B-ALL	Reinduction(4weeks)	Reinduction -\> Blinatumomab-Salvage 1st -\> Blinatumomab-Salvage 2nd -\> HSCT
Very high Risk with B-ALL	Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks	Reinduction -\> Blinatumomab-Salvage 1st -\> Blinatumomab-Salvage 2nd -\> HSCT
Very high Risk with B-ALL	Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks	Reinduction -\> Blinatumomab-Salvage 1st -\> Blinatumomab-Salvage 2nd -\> HSCT
Very high Risk with B-ALL	Intensification course	Reinduction -\> Blinatumomab-Salvage 1st -\> Blinatumomab-Salvage 2nd -\> HSCT
T-ALL	Reinduction(4weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> HSCT
T-ALL	Cosolodation 1st(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> HSCT
T-ALL	Consolidation 2nd(3weeks)	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> HSCT
T-ALL	Stem Cell Transplantation	Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> HSCT

Primary Outcome Measures

Name	Time	Method
Safety/Efficacy	through study completion, an average of 9 year	Patients with relapsed acute lymphoblastic leukemia are being treated after sorted into groups with their potential risk, and disease-free survival rate will be checked.

Secondary Outcome Measures

Name	Time	Method
Death rate related to toxicity	through study completion, an average of 9 year	Comparing remission rate and occurrence rate of toxicity during re-intervention therapy after changed schedules of idarubicin
Disease-free survival rate (Blinatumomab)	through study completion, an average of 9 year	Blinatumomab is used before transplantation to patients with high-risk group, and then disease-free survival rate will be compared before and after
Disease-free survival rate (standard risk)	through study completion, an average of 9 year	Patients with standard risk who are not eligible for allogenic stem cell transplantation are given consolidation and maintenance therapies, and disease-free survival rate will compared before and after
Disease-free survival rate (Comparing minimal residual disease)	through study completion, an average of 9 year	Comparing minimal residual disease negative rate with the study before by adding blinatumomab to patients in high risk group
Death rate related to treatment	through study completion, an average of 9 year	Children and adolescents who have relapsed acute lymphoblastic leukemia re administered different treatments depending on their assigned groups, and disease-free survival rate will be compared before and after
Toxicity rate during consolidation therapy	through study completion, an average of 9 year	Checking occurence rate of toxicity related to treatment during consolidation for patients in low-risk group

Trial Locations

Locations (7)

Seoul saint Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of