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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ho Joon Im; Phone Number: +82-10-6231-1573; Email: hojim@amc.seoul.kr

Study Locations

• Korea, Republic of
  • Hwasun, Korea, Republic of, 58128
    • Recruiting
    • Chonnam National University Hwasun Hospital
    • Contact: Hee Jo Baek, Ph.D; Phone Number: +82-10-4607-1784; Email: swan93@naver.com
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Hyoung Jin Kang, Professor
  • 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
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Seung Min Hahn, Professor; Phone Number: +82-10-8821-5201; Email: bluenile88@yuhs.ac
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul Saint Mary's Hospital
    • Contact: Jae Wook Lee, Professor; Phone Number: +821026460668; 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:

• 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 < 2 years - Male (0.6) Female (0.6) 2 to < 6 years - Male (0.8) Female (0.8) 6 to < 10 years - Male (1) Female (1) 10 to < 13 years - Male (1.2) Female (1.2) 13 to < 16 years - Male (1.5) Female (1.4)

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

• Adequate Liver Function defined as a direct bilirubin <3.0 mg/dL
• Adequate Cardiac Function defined as: Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by echocardiogram
• Lansky (age < 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' 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 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Risk group with B-ALL; 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); 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; Drug: Cosolodation 1st(3weeks); 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; Drug: Consolidation 2nd(3weeks); 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; Drug: Intensification course; Etoposide: 100 mg/m2 on day 1, 2, 3, Ifosfamide 3.4 g/m2 on day 1, 2, 3 Oral 6-mercaptopurine 50 mg/m2/day PO (days 1-14), Methotrexate: 25 mg/m2 on day 1, 8, TIT on day 1 Ara-C 1.0 g/m2 (days 1-3), Idarubicin: 5mg/m2 (days 1- 3) 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; Drug: Maintenance(12 Weeks/Cycle); 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)
Experimental: High Risk group with B-ALL; Reinduction -> Consolidation 1st -> Consolidation 2nd -> Blinatumomab 1st -> Blinatumomab 2nd -> HSCT	Drug: Reinduction(4weeks); 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; Drug: Cosolodation 1st(3weeks); 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; Drug: Consolidation 2nd(3weeks); 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; Drug: Blinatumomab 1st(High Risk Group)_4 Weeks; 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); Drug: Blinatumomab 2nd (High Risk Group)_4 Weeks; 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); Procedure: Stem Cell Transplantation; All matters related to hematopoietic stem cell transplantation are subject to each institution's practice.
Experimental: Very high Risk with B-ALL; Reinduction -> Blinatumomab-Salvage 1st -> Blinatumomab-Salvage 2nd -> HSCT	Drug: Reinduction(4weeks); 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; Drug: Intensification course; Etoposide: 100 mg/m2 on day 1, 2, 3, Ifosfamide 3.4 g/m2 on day 1, 2, 3 Oral 6-mercaptopurine 50 mg/m2/day PO (days 1-14), Methotrexate: 25 mg/m2 on day 1, 8, TIT on day 1 Ara-C 1.0 g/m2 (days 1-3), Idarubicin: 5mg/m2 (days 1- 3) 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; Drug: Blinatumomab-Salvage 1st (Very High Risk Group)_4 Weeks; 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); Drug: Blinatumomab-Salvage 2nd (Very High Risk Group)_4 Weeks; 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)
Experimental: T-ALL; Reinduction -> Consolidation 1st -> Consolidation 2nd -> HSCT	Drug: Reinduction(4weeks); 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; Drug: Cosolodation 1st(3weeks); 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; Drug: Consolidation 2nd(3weeks); 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; Procedure: Stem Cell Transplantation; All matters related to hematopoietic stem cell transplantation are subject to each institution's practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival rate (Blinatumomab)	Blinatumomab is used before transplantation to patients with high-risk group, and then disease-free survival rate will be compared before and after	through study completion, an average of 9 year
Disease-free survival rate (standard risk)	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	through study completion, an average of 9 year
Disease-free survival rate (Comparing minimal residual disease)	Comparing minimal residual disease negative rate with the study before by adding blinatumomab to patients in high risk group	through study completion, an average of 9 year
Death rate related to treatment	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	through study completion, an average of 9 year
Death rate related to toxicity	Comparing remission rate and occurrence rate of toxicity during re-intervention therapy after changed schedules of idarubicin	through study completion, an average of 9 year
Toxicity rate during consolidation therapy	Checking occurence rate of toxicity related to treatment during consolidation for patients in low-risk group	through study completion, an average of 9 year

Collaborators and Investigators

• Sponsor: Ho Joon Im
• Collaborators: Samsung Medical Center; Seoul St. Mary's Hospital; Chonnam National University Hospital; Seoul National University Hospital; Severance Hospital; Pusan National University Yangsan Hospital
• Investigators: Study Chair: Ho Joon Im, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2024
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: combination chemotherapy
• 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; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Bispecific; Blinatumomab
• Other Study ID Numbers: KPHOG_T1RALL2201

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