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

Study Overview
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Brief Summary
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This study is open-label, multi-center, prospective study, which targets childhood patients with recurred acute lymphostatic leukemia including recurrence around marrow. This study is designed to administer Idarubicin for Reinduction stage. Patients with recurrence are sorted into groups with their potential risk, and depending on their recurrence point, time, reaction to treatment etc, they are sorted into low-risk group, high-risk group, and highest-risk group. Patients with high-risk group are going to be given blinatumomab at consolidation stage before hematopoietic stem cell transplantation. Patients with low-risk group who are not suitable for hematopoietic stem cell transplantation are going to be maintaining maintenance therapy for 2 years for chemotherapy.

Detailed Description
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Baseline demographics: Sex, Birth date, expire date (last follow-up date for the survivals) Diagnosis of Acute lymphoblastic leukemia and treatment history: Diagnosed date, treatment history (Stem cell transplantation history, Administration of Blinatumomab history, recurrence date to check whether recurred within a month after received 4 therapies of induction) Tests before actual administration: EKG and or Echo, Blood sample: Complete Blood Count/Diff/Platelets, Chemistry, Urinalysis, HIV, human chorionic gonadotrophin [female], Minimal Residual Disease[Next-generation sequencing, after induction / could be done after 1st, 2nd consolidation therapy] Bone marrow aspiration

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

Conditions
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Acute Lymphoid Leukemia

Intervention / Treatment
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* Drug: Blincyto


Participation Criteria
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Eligibility Criteria
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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 Patients who relapsed within a month after completing 4 therapies 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 Patients with mixed phenotype leukemia Patients with genetic syndrome: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome bone marrow failure syndrome Patients with 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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Interventional Model Description: Blinatumomab Cycle 1,2 S cycle 1,2 (High risk group) is going to be given for 4 weeks before transplantation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single group study<br>Apply Blinatumomab Cycle 1,2, S cycle 1, 2 (High Risk Group)- 4 weeks to patients before transplantation | Drug: Blincyto<br>* Vincristine 1.5mg/m2, L-asparaginase 6,000 IU/m2 Idarubicin 10mg/m2 will be administered for induction therapy. Ifosfamide 1.8g/m2 Etoposide 100mg/m2 will be administered for consolidation therapy, then patients will be sorted into groups depend on their potential risk and Blinatumomab IV will be administered over 28 days. Intensification course will be administered 4 times repeated. 1. etoposide 100mg/m2 Ifosfamide 3.4g/m2 with MESNA / 2.oral 6-mercaptopurine 50mg/m2, methotrexate 25mg/m2 / 3.Ara-C 1.0g/m2, Idarubicin 5mg/m2 / 4.vincristine 2mg/m2 are the courses for repetition.<br>* Other names: Blinatumomab (Amgen);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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combination chemotherapy