Leukemia, Lymphoid
Conditions
Brief summary
This clinical trial is an open-label, multicenter, prospective phase 2 clinical trial targeting pediatric leukemia patients of infant age. The goal is to improve survival rates by varying the presence or absence of chemotherapy and hematopoietic stem cell transplantation based on genetic characteristics at the time of diagnosis and minimal residual disease (MRD) values measured by various methods after treatment. In addition, by clearly defining the patient group that requires hematopoietic stem cell transplantation, it is expected that the role of hematopoietic stem cell transplantation in infantile leukemia, for which there have been various guidelines for hematopoietic stem cell transplantation, can be confirmed. Additionally, due to the characteristics of infants, this study aim to identify long-term sequelae or prognosis related to treatment by prospectively collecting side effect data related to treatment during and after treatment.
Detailed description
Infant leukemia patients are classified into low/intermediate/high risk groups and hematopoietic stem cell transplantation is performed after chemotherapy or chemotherapy as shown in the schema below. * Low risk group : Induction chemotherapy-Low Risk Consolidation chemotherapy 1\ 4 - Maintenance chemotherapy * Intermediate risk group : Induction chemotherapy-High Risk Consolidation chemotherapy 1\ 4 - Maintenance chemotherapy * High risk group : Induction chemotherapy-High Risk Consolidation chemotherapy 1\ 4 - hematopoietic stem cell transplantation
Interventions
DRUGConsolidation #4(without daunorubicin)
1. Induction chemotherapy(5wks) : Prednisolone, Dexamethasone, Vincristine, Daunorubicin, L-asparaginase, Cytarabine, intrathecal cytarabine, intrathecal methotrexate 2. Low Risk Cosolidation 1 chemotherapy(3wks) : Cytarabine, Etoposide, Cyclophosphamide, intrathecal methotrexate 3. Low Risk Cosolidation 2 chemotherapy(3wks) : Methotrexate, 6-mercaptopurine, intrathecal methotrexate 4. Low Risk Cosolidation 3 chemotherapy(3wks) : Cytarabine, L-asparaginase, intrathecal methotrexate 5. Low Risk Cosolidation 3 chemotherapy(8wks) : Dexamethasone, Vincristine, Daunorubicin, Cytarabine, Cyclophosphamide, 6-mercaptopurine, intrathecal methotrexate 6. Maintenance chemotherapy(about 2yrs) : Vincristine, Dexamethasone, 6-mercaptopurine, intrathecal methotrexate
DRUGConsolidation #4(with daunorubicin)
1. Induction chemotherapy(5wks) : Prednisolone, Dexamethasone, Vincristine, Daunorubicin, L-asparaginase, Cytarabine, intrathecal cytarabine, intrathecal methotrexate 2. High Risk Cosolidation 1 chemotherapy(3wks) : Cytarabine, Etoposide, Cyclophosphamide, Daunorubicin intrathecal methotrexate 3. High Risk Cosolidation 2 chemotherapy(3wks) : Methotrexate, 6-mercaptopurine, intrathecal methotrexate 4. High Risk Cosolidation 3 chemotherapy(3wks) : Cytarabine, L-asparaginase, intrathecal methotrexate 5. High Risk Cosolidation 3 chemotherapy(8wks) : Dexamethasone, Vincristine, Daunorubicin, Cytarabine, Cyclophosphamide, 6-mercaptopurine, intrathecal methotrexate 6. Maintenance chemotherapy(about 2yrs) : Vincristine, Dexamethasone, 6-mercaptopurine, intrathecal methotrexate
DRUGAllogeneic hematopoietic stem cell transplantation after Consolidation #4(with daunorubicin)
1. Induction chemotherapy(5wks) : Prednisolone, Dexamethasone, Vincristine, Daunorubicin, L-asparaginase, Cytarabine, intrathecal cytarabine, intrathecal methotrexate 2. High Risk Cosolidation 1 chemotherapy(3wks) : Cytarabine, Etoposide, Cyclophosphamide, Daunorubicin intrathecal methotrexate 3. High Risk Cosolidation 2 chemotherapy(3wks) : Methotrexate, 6-mercaptopurine, intrathecal methotrexate 4. High Risk Cosolidation 3 chemotherapy(3wks) : Cytarabine, L-asparaginase, intrathecal methotrexate 5. High Risk Cosolidation 3 chemotherapy(8wks) : Dexamethasone, Vincristine, Daunorubicin, Cytarabine, Cyclophosphamide, 6-mercaptopurine, intrathecal methotrexate 6. Allogeneic hematopoietic stem cell transplantation
Sponsors
Yonsei University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Low risk group : KMT2A wild type & minimal residual disease(MRD) (-) after consolidation 1 * Intermediate risk group : Intermediate risk (If one of the two cases below applies) * KMT2A: MLL mutation (+) & minimal residual disease (MRD) (-) after consolidation 1 * KMT2A: wild type & minimal residual disease (MRD) (+) after consolidation 1 * High risk group : Somatic KMT2A mutation (+) & minimal residual disease (MRD) (+) after consolidation 1
Eligibility
Sex/Gender
ALL
Age
No minimum to 2 Years
Healthy volunteers
No
Inclusion criteria
* The age of diagnosis is less than 1 year old * The disgnosisi of ALL or ALAL(lymphoid predominant) * Informed consent of the parents(guardians) before participation in this study
Exclusion criteria
* Burkitt leukemia/lymphoma or mature B-cell leukemia * Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or other bone marrow failure syndrome, hematopoietic stem cell transplantation * Relapsed infant leukemia * Participants with contraindication to medication * Administered systemic steroid therapy within 4 weeks prior to this study (However, steroid administration is allowable in oncologic emergencies only after the subject's disease diagnosis and risk group classification are completed.) * Participants in other interventional studies other than this protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-years Overall survival(OS) rate | 3-years | The 3-years overall survival rate defined as the percentage of subject in a treatment group who are alive three years after the start of treatm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 5years | The overall survival rate defined as the percentage of subject in a treatment group who are alive five years after the start of treatment. |
| Event Free Survial(EFS) | 3-years and 5-years | EFS is defined as the period from study enrollment until disease progression, including hematological recurrence of ALL, development of secondary malignancy, or death from any causes, whichever occurs earlier. |
| The rate of hematopoietic stem cell transplant patients by risk group | Up to 5years | through study completion, an average of 1 year |
| recurred rate | Up to 5years | As a the period from enrollment to disease progression/recurrence |
| Death rate related to infusion | Up to 5years | The time until defined by date of drug-related mortality from the date of 1st infusion |
Countries
South Korea
Outcome results
None listed