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

ConditionAcute Lymphoid Leukemia

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age1-22

SponsorHo Joon Im

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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)

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

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
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
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
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)
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)
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)
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)
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
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)
Stem Cell Transplantation
Procedure/Surgery
All matters related to hematopoietic stem cell transplantation are subject to each institution's practice.

Treatment groups

90 Participants

are divided into 4 treatment groups

Group A: Standard Risk group with B-ALLExperimental treatment 5 interventions

Group B: High Risk group with B-ALLExperimental treatment 6 interventions

Group C: Very high Risk with B-ALLExperimental treatment 4 interventions

Group D: T-ALLExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

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.

Time frame