Treatment of Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia in Children

Sponsor

Hee Young Ju (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06099366

Collaborator

(none)

116

Enrollment

Arms

119.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for standard risk acute lymphoblastic leukemia in children and adolescents.

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia in Children	Drug: induction: vincristine, L-asparaginase, dexamethasone, intrathecal Ara-C, intrathecal Methotrexate Drug: Consolidation: Vincristine, Mecaptopurine, Intrathecal Methotrexate Drug: Consolidation: Vincristine, Mecaptopurine, Cyclophosphamide, Cytarabine, L-asparaginase, Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Mercaptopurine, Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, Mercaptopurine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Drug: Maintenance: Vincristine, Mercaptopurine, Methotrexate, Dexamethasone, Intrathecal Methotrexate	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

116 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Treatment of Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia in

Anticipated Study Start Date :

Jan 15, 2024

Anticipated Primary Completion Date :

Dec 31, 2033

Anticipated Study Completion Date :

Dec 31, 2033

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Standard-low (SL) Induction-> SL Consolidation(4weeks)-> Interim Maintenance 1st-> Delayed Intesificaion-> Interim Maintenance 2nd-> Maintenance	Drug: induction: vincristine, L-asparaginase, dexamethasone, intrathecal Ara-C, intrathecal Methotrexate vincristine 1.5mg/m2 L-asparaginase 6,000U/m2 Dexamethasone 6mg/m2 Intrathecal Cytarabine Intrathecal Methotreate Drug: Consolidation: Vincristine, Mecaptopurine, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mecaptopurine 50mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 L-asparaginase 6,000U/m2 Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Intrathecal Methotrexate Vincristine 1.5mg/m2 Methotrexate 5,000mg/m2 Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, Mercaptopurine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 L-asparaginase 6,000IU/m2 Doxorubicin 25mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 Dexamethasone 10mg/m2 Intrathecal Methotrexate Drug: Maintenance: Vincristine, Mercaptopurine, Methotrexate, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 Methotrexate 20mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate
Experimental: Standard-average (SA) Induction-> SH Consolidation(8weeks)-> Interim Maintenance 1st-> Delayed Intesificaion-> Interim Maintenance 2nd-> Maintenance	Drug: induction: vincristine, L-asparaginase, dexamethasone, intrathecal Ara-C, intrathecal Methotrexate vincristine 1.5mg/m2 L-asparaginase 6,000U/m2 Dexamethasone 6mg/m2 Intrathecal Cytarabine Intrathecal Methotreate Drug: Consolidation: Vincristine, Mecaptopurine, Cyclophosphamide, Cytarabine, L-asparaginase, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mecaptopurine 50mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 L-asparaginase 6,000IU/m2 Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Intrathecal Methotrexate Vincristine 1.5mg/m2 Methotrexate 5,000mg/m2 Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, Mercaptopurine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 L-asparaginase 6,000IU/m2 Doxorubicin 25mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 Dexamethasone 10mg/m2 Intrathecal Methotrexate Drug: Maintenance: Vincristine, Mercaptopurine, Methotrexate, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 Methotrexate 20mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate
Experimental: Standard-high 1 (SH1) Induction-> SL Consolidation(4weeks)-> SH Consolidattion(4weeks)-> Interim Maintenance 1st-> Delayed Intesificaion 1st-> Interim Maintenance 2nd-> Delayed Intestificaion 2nd-> Maintenance	Drug: induction: vincristine, L-asparaginase, dexamethasone, intrathecal Ara-C, intrathecal Methotrexate vincristine 1.5mg/m2 L-asparaginase 6,000U/m2 Dexamethasone 6mg/m2 Intrathecal Cytarabine Intrathecal Methotreate Drug: Consolidation: Vincristine, Mecaptopurine, Cyclophosphamide, Cytarabine, L-asparaginase, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mecaptopurine 50mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 L-asparaginase 6,000IU/m2 Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Mercaptopurine, Intrathecal Methotrexate Vincristine 1.5mg/m2 Methotrexate 5,000mg/m2 Mecaptopurine: 25mg/m2 Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 L-asparaginase 6,000IU/m2 Doxorubicin 25mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 100mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate Drug: Maintenance: Vincristine, Mercaptopurine, Methotrexate, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 Methotrexate 20mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate
Experimental: Standard-high 2 (SH2) Induction-> SH Consolidattion(8weeks)-> Interim Maintenance 1st-> Delayed Intesificaion 1st-> Interim Maintenance 2nd-> Delayed Intestificaion 2nd-> Maintenance	Drug: induction: vincristine, L-asparaginase, dexamethasone, intrathecal Ara-C, intrathecal Methotrexate vincristine 1.5mg/m2 L-asparaginase 6,000U/m2 Dexamethasone 6mg/m2 Intrathecal Cytarabine Intrathecal Methotreate Drug: Consolidation: Vincristine, Mecaptopurine, Cyclophosphamide, Cytarabine, L-asparaginase, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mecaptopurine 50mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 75mg/m2 L-asparaginase 6,000IU/m2 Intrathecal Methotrexate Drug: Interim Maintenance(IM): Vincristine, Methotrexate, Mercaptopurine, Intrathecal Methotrexate Vincristine 1.5mg/m2 Methotrexate 5,000mg/m2 Mecaptopurine: 25mg/m2 Intrathecal Methotrexate Drug: Delayed Intesification(DI): Vincristine, L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 L-asparaginase 6,000IU/m2 Doxorubicin 25mg/m2 Cyclophosphamide 1,000mg/m2 Cytarabine 100mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate Drug: Maintenance: Vincristine, Mercaptopurine, Methotrexate, Dexamethasone, Intrathecal Methotrexate Vincristine 1.5mg/m2 Mercaptopurine 50mg/m2 Methotrexate 20mg/m2 Dexamethasone 6mg/m2 Intrathecal Methotrexate

Outcome Measures

Primary Outcome Measures

5-year event free survival rate [Up to 5-years]

Secondary Outcome Measures

Confirmation of the therapeutic effect of the initial treatment response [Up to 5-years]
Relapse-free survival between two groups(NGS-MRD positive vs. NGS MRD negative after induction) offsets by NGS MRD based stratified treatment
Disease prognosis-related factor [Up to 5-years]
Relapse-free survival according to presence or absence of known good prognosis factors(high hyperdilpoidy, ETV6/RUNX1, Trisomy 4/10/17) have no clinical significance when NGS MRD based stratified treatment is performed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 9 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newly diagnosed pediatric/adolescent acute lymphomblastic leukemia patient with NCL standard risk that stratifies all 1-5 of following

1 year old ≤ Age < 10 years old
white blood cell at initial diagnosis < 5x10^10/L (50,000uL)
CNS 1 or 2
No testis involvement
Satisfaction of following organ functions

Kidney function (satisfies i or ii)

Creatinine clearance (or radioisotope-measured GFR) ≥ 70mL/min/1.73m2

Creatinine value according to age/sec satisfies the following: 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

Liver function i. Direct bilirubin < 3.0mg/dL
Cardiac function i. Shortening fraction ≥ 27% confirmed by cardiac echography

Ejection fraction ≥ 50% confirmed by cardiac echography

Exclusion Criteria:

Steroid administration within 2 weeks before the diagnosis
t(9;22) or t(4;11)(q11;q23) or chromosome < 44 or iAMP21 or t(17;19)/TCF3-HLF
One of the following syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or other bone marrow failure syndrome
Burkitt leukemia/lymphoma
When the clinical trial subject(or legal representative) does not consent or is unable to give written consent