Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2019 Pilot

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

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.

Study Overview

• Status: Recruiting
• Conditions: Childhood Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander I. Karachunskiy, Professor,MD; Phone Number: +7-926-218-84-09; Email: info@mbstudy.net
• Study Contact Backup: Name: Julia V. Roumiantseva, MD, PhD; Phone Number: +7-903-730-39-78; Email: j.roumiantseva@mbstudy.net

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Dmitry Rogachev National Medical Research Centre of Pediatric Hematology, Oncology and Immunology
  • Moscow, Russian Federation
    • Recruiting
    • National Medical Research Center of Oncology named after N.N. Blokhin
  • Moscow, Russian Federation
    • Recruiting
    • Russian Children's Clinic Hospital; Pirogov Russian National Research Medical University
  • Saint Petersburg, Russian Federation
    • Recruiting
    • Almazov National Medical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Age at diagnosis at 1 to 18 years.
2. The start of induction therapy within a time interval of study recruitment phase.
3. 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).
4. CD19 expression on tumor cells.
5. Informed consent of the patient parents (guardians)

Exclusion Criteria:

1. Any non-compliance with the inclusion criteria.
2. ALL is a second malignancy.
3. There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.);
4. The patient was treated before for a long time with cytotoxic drugs.
5. Initial CNS (central nervous system) involvement (status CNSII or CNSIII).
6. Initial leukocyte count ≥100×109/L (except for patients with significant translocations).
7. Patients not achieved cytological remission after induction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinatumomab; Consolidation therapy with Blinatumomab administration	Drug: Blinatumomab; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Investigators: Principal Investigator: Alexander I. Karachunskiy, Professor,MD, Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Children; Immunotherapy; Chemotherapy; Blinatumomab; Acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: ALL-MB 2019 Pilot

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No