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

NCT05827549 | Recruiting Phase 2

• 1 other identifier: KPHOG_T1RALL2201
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 7

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.

Conditions

Acute Lymphoid Leukemia

Keywords

combination chemotherapy

Outcome Measures

Primary Outcomes (1)

• Safety/Efficacy

  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.

  through study completion, an average of 9 year

Secondary Outcomes (6)

• Disease-free survival rate (Blinatumomab)

  through study completion, an average of 9 year

• Disease-free survival rate (standard risk)

  through study completion, an average of 9 year

• Disease-free survival rate (Comparing minimal residual disease)

  through study completion, an average of 9 year

• Death rate related to treatment

  through study completion, an average of 9 year

• Death rate related to toxicity

  through study completion, an average of 9 year

Study Arms (4)

Standard Risk group with B-ALL

EXPERIMENTAL

Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Repeat the Intensification course in parentheses 3 times(Intensification 1st -\> Intensification 2nd -\> Intensification 3rd -\> Intensification 4th) -\> Maintenance

Drug: Reinduction(4weeks); Drug: Cosolodation 1st(3weeks); Drug: Consolidation 2nd(3weeks); Drug: Intensification course; Drug: Maintenance(12 Weeks/Cycle)

High Risk group with B-ALL

EXPERIMENTAL

Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> Blinatumomab 1st -\> Blinatumomab 2nd -\> HSCT

Drug: Reinduction(4weeks); Drug: Cosolodation 1st(3weeks); Drug: Consolidation 2nd(3weeks); Drug: Blinatumomab 1st(High Risk Group)_4 Weeks; Drug: Blinatumomab 2nd (High Risk Group)_4 Weeks; Procedure: Stem Cell Transplantation

Very high Risk with B-ALL

EXPERIMENTAL

Reinduction -\> Blinatumomab-Salvage 1st -\> Blinatumomab-Salvage 2nd -\> HSCT

Drug: Reinduction(4weeks); Drug: Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks; Drug: Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks; Drug: Intensification course

T-ALL

EXPERIMENTAL

Reinduction -\> Consolidation 1st -\> Consolidation 2nd -\> HSCT

Drug: Reinduction(4weeks); Drug: Cosolodation 1st(3weeks); Drug: Consolidation 2nd(3weeks); Procedure: Stem Cell Transplantation

Interventions

Reinduction(4weeks) DRUG

Prednisolone 60 mg/m2/day tid days 1-28, Vincristine 1.5 mg/m2 on days 1, 8, 15, 22, L-asparaginase 6,000 IU/m2(days 2-4 start, total 9 doses for 3 weeks), Idarubicin 10 mg/m2 on days 1, 8, (15\~17), IT Ara-C on days 1, IT MTX on days 8, 29

High Risk group with B-ALL; Standard Risk group with B-ALL; T-ALL; Very high Risk with B-ALL

Cosolodation 1st(3weeks) DRUG

Ifosfamide: 1.8 g/m2 (days 1, 2, 3, 4, 5), Etoposide: 100 mg/m2 (days 1, 2, 3, 4, 5), IT MTX on day 1

High Risk group with B-ALL; Standard Risk group with B-ALL; T-ALL

Consolidation 2nd(3weeks) DRUG

MTX: 500 mg/m2 over 30 min followed by 1,000 mg/m2 over 23.5 hr (day 1), Ara-C: 3,000 mg/m2/dose (day 2, 3), IT MTX on day 1

High Risk group with B-ALL; Standard Risk group with B-ALL; T-ALL

Blinatumomab 1st(High Risk Group)_4 Weeks DRUG

Blinatumomab 15 mcg/m²/day(Days: 1-28), Dexamethasone 5 mg/m2/dose on Day 1, IT MTX on day 15, 29 (CNS 1, 2 patients), TIT on day 15, 29 (CNS 3 patient)

High Risk group with B-ALL

Blinatumomab 2nd (High Risk Group)_4 Weeks DRUG

Blinatumomab 15 mcg/m²/day(Days: 1-28), IT MTX on day 15, 29 (CNS 1, 2 patients), TIT on day 15, 29 (CNS 3 patient)

High Risk group with B-ALL

Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks DRUG

Blinatumomab 9 mcg/day(Weight ≥ 45kg) or 5 mcg/m²/day(Weight \< 45kg) on 1-7 days, 28 mcg/day(Weight ≥ 45kg) or 15 mcg/m²/day(Weight \< 45kg) on 8-28 days, Dexamethasone 5 mg/m2/dose on day 1 and day 8, IT MTX on day 15, 29 (CNS 1, 2 patients), TIT on day 15, 29 (CNS 3 patient)

Very high Risk with B-ALL

Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks DRUG

Blinatumomab 28 mcg/day(Weight ≥ 45kg) or 15 mcg/m²/day(Weight \< 45kg) on 1-28 days, IT MTX on day 15, 29 (CNS 1, 2 patients), TIT on day 15, 29 (CNS 3 patient)

Very high Risk with B-ALL

Intensification course DRUG

\<Intensification 1st(3 Weeks)\> Etoposide: 100 mg/m2 on day 1, 2, 3, Ifosfamide 3.4 g/m2 on day 1, 2, 3 \<Intensification 2nd(2 Weeks)\> Oral 6-mercaptopurine 50 mg/m2/day PO (days 1-14), Methotrexate: 25 mg/m2 on day 1, 8, TIT on day 1 \<Intensification 3rd(3 Weeks)\> Ara-C 1.0 g/m2 (days 1-3), Idarubicin: 5mg/m2 (days 1- 3) \<Intensification 4th(2 Weeks)\> Dexamethasone 8 mg/m2/day on days 1-14, Vincristine 2 mg/m2 on days 1 and 8, L-asparaginase 10,000 IU/m2 on days 1 and 8

Standard Risk group with B-ALL; Very high Risk with B-ALL

Maintenance(12 Weeks/Cycle) DRUG

Prednisolone: 15 mg/m²/dose(Days 1-5, 29-33, 57-61), Vincristine: 1.5 mg/m²/dose(Day 1, 29, 57), Oral 6-mercaptopurine: 50 mg/m²/dose (Days 1-84), Methotrexate: 20 mg/m²/dose (Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78), Intrathecal methotrexate (Day 1)

Standard Risk group with B-ALL

Stem Cell Transplantation PROCEDURE

All matters related to hematopoietic stem cell transplantation are subject to each institution's practice.

High Risk group with B-ALL; T-ALL

Eligibility Criteria

• Age: 1 Year - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• st 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ho Joon Im: lead
• Samsung Medical Center: collaborator
• Seoul National University Hospital: collaborator
• Severance Hospital: collaborator
• Chonnam National University Hospital: collaborator
• Pusan National University Yangsan Hospital: collaborator
• Seoul St. Mary's Hospital: collaborator

Study Sites (7)

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Seoul saint Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Maintenance; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Health Care Facilities Workforce and Services; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ho Joon Im

  Asan Medical Center

  STUDY CHAIR

Central Study Contacts

Ho Joon Im

CONTACT

+82-10-6231-1573; hojim@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: April 25, 2023
• Study Start: April 4, 2024
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (7)