Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2019 Pilot

Study Overview
=================
Brief Summary
-----------------
THE PURPOSE OF THE STUDY is to optimize the therapy of patients with primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) by including monoclonal bispecific antibodies in post-induction treatment with simultaneous reduction of chemotherapy. QUESTIONS AND OBJECTIVES OF THE STUDY: to determine the efficacy and feasibility of chemotherapy and immunotherapy combination in comparison with standard PCT in children and adolescents with newly diagnosed BCP-ALL; to determine the safety and toxicity of chemotherapy and immunotherapy combination in comparison with standard PCT in children and adolescents with newly diagnosed BCP-ALL; to determine the possibility of chemotherapy reducing when immunotherapy is included in the treatment regimen without loss of effectiveness; to determine the possibility of reducing the maintenance therapy duration to 1 year when immunotherapy is included in the treatment regimen without loss of effectiveness.

Official Title
-----------------
Treatment of Children and Adolescents With Primary B-precursor Acute Lymphoblastic Leukemia With Combination Chemotherapy and Immunotherapy

Conditions
-----------------
Childhood Acute Lymphoblastic Leukemia

Intervention / Treatment
-----------------
* Drug: Blinatumomab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: This study included patients with B-cell precursor ALL (BCP-ALL) diagnosed or confirmed in one of the clinics participating in the study. Also following criteria should be considered at the diagnosis for each case: Age at diagnosis at 1 to 18 years. The start of induction therapy within a time interval of study recruitment phase. The diagnosis of BCP-ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow in the reference laboratories of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (D. Rogachev NMRCPHOI). CD19 expression on tumor cells. Informed consent of the patient parents (guardians) Exclusion Criteria: Any non-compliance with the inclusion criteria. ALL is a second malignancy. There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.); The patient was treated before for a long time with cytotoxic drugs. Initial CNS (central nervous system) involvement (status CNSII or CNSIII). Initial leukocyte count ≥100×109/L (except for patients with significant translocations). Patients not achieved cytological remission after induction

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinatumomab<br>Consolidation therapy with Blinatumomab administration | Drug: Blinatumomab<br>* Blinatumomab, intravenously, as continuous 24 hours infusion 1-7 days - 5 μg/m2/day, 8-28 day - 15 μg/m2/day 1 course after induction treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal residual disease level |  | On the last day of the blinatumomab course, on average at 11 weeks of protocol | 
| Minimal residual disease level |  | 6 months after starting maintenance therapy | 
| Minimal residual disease level |  | 1 year after starting maintenance therapy | 
| Event-free survival |  | 3 years after study start | 
| Event-free survival |  | 5 years after study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years after study start | 
| Overall survival |  | 5 years after study start | 
| Cumulative incidence of relapse |  | 3 years after study start | 
| Cumulative incidence of relapse |  | 5 years after study start | 
| Remission death rate |  | 3 years after study start | 
| Remission death rate |  | 5 years after study start | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute lymphoblastic leukemia, Children, Chemotherapy, Immunotherapy, Blinatumomab