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

Ho Joon Im

Status and phase: Enrolling; Phase 2

Conditions: Acute Lymphoid Leukemia

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05827549

KPHOG_T1RALL2201

Details and patient eligibility

About

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.

Full 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

Enrollment: 90 estimated patients

Sex: All

Ages: 1 to 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 4 patient groups

Standard Risk group with B-ALL

Experimental group

Description:

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

Treatment:

Drug: Consolidation 2nd(3weeks)

Drug: Cosolodation 1st(3weeks)

Drug: Intensification course

Drug: Reinduction(4weeks)

Drug: Maintenance(12 Weeks/Cycle)

High Risk group with B-ALL

Experimental group

Description:

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

Treatment:

Drug: Blinatumomab 1st(High Risk Group)_4 Weeks

Drug: Consolidation 2nd(3weeks)

Drug: Cosolodation 1st(3weeks)

Procedure: Stem Cell Transplantation

Drug: Blinatumomab 2nd (High Risk Group)_4 Weeks

Drug: Reinduction(4weeks)

Very high Risk with B-ALL

Experimental group

Description:

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

Treatment:

Drug: Intensification course

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

Drug: Reinduction(4weeks)

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

T-ALL

Experimental group

Description:

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

Treatment:

Drug: Consolidation 2nd(3weeks)

Drug: Cosolodation 1st(3weeks)

Procedure: Stem Cell Transplantation

Drug: Reinduction(4weeks)