Combined Immuno-chemotherapy for Patients With B-linear Acute Lymphoblastic Leukemia Diagnosed From 0 to 365 Days of Life (ALL-Baby-2021)

NCT05029531 | Recruiting Phase 3

• 1 other identifier: NCHPOI-2021-03
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The innovation of this protocol is the risk-adapted choice of therapy and the use of a combination of chemotherapy with immunotherapy and hematopoietic stem cell transplantation for patients with risk factors. Investigators have proposed a two-stage stratification into risk groups: Initially:

• Standard risk: patients with no rearrangement of the KMT2A gene.
• Intermediate risk: patients with rearrangement of the KMT2A gene without damage to the central nervous system.
• High risk: patients with rearrangement of the KMT2A gene with lesions of the central nervous system. According to the results of induction therapy:
• The high-risk group includes patients from the standard risk group with an MRD level of more than 0.1% after the induction course and from the intermediate risk group with MRD-positive (PCR) after HR1 block.
• The allocation of children in the first year of life without the rearranged KMT2A gene into a separate group seems to be logical, since the prognosis in this group is better than in children with the rearranged KMT2A gene. In this protocol, non-intensive therapy with consolidations and maintenance therapy remains for those who achieve a low MRD level (less than 0.1%) after a course of induction. The rest of the patients move into a high-risk group: they receive blinatumomab and HSCT.
• The concept of therapy for patients at intermediate risk is based on the rate at which MRD-negativity is achieved: standard consolidation and maintenance therapy for those who became MRD-negative at the end of induction, "block" chemotherapy for those who were positive at the end of induction, but achieved negativity after HR1 block, blinatumomab with HSCT for those who have preserved the MRD after the HR1 block.
• For high-risk patients, a combination of immunotherapy (blinatumomab - a bispecific CD3 / CD19 T-cell activator) and HSCT in the first remission was chosen.

Conditions

Acute Lymphoblastic Leukemia, Pediatric; ALL, Infants

Keywords

Acute lymphoblastic leukemia; children; infant; treatment сhemotherapy; Immunotherapy; Blinatumomab; Stemm Cell Transplantation

Outcome Measures

Primary Outcomes (2)

• event free survival

  4 years after the start of therapy

• overal survival

  4 years after the start of therapy

Secondary Outcomes (4)

• risk of relapse

  3 years after the start of therapy

• frequency of achieving MRD-negative remission

  after a course of induction up to 1 week

• frequency of achieving MRD-negative remission

  after a course of consolidation up to 1 week

• mortality associated with HSCT

  2 years post HSCT

Study Arms (1)

intervention/treatment

EXPERIMENTAL

Combination Product: the risk-adapted choice of therapy and the use of a combination of chemotherapy with immunotherapy and hematopoietic stem cell transplantation for patients with risk factors.

Interventions

the risk-adapted choice of therapy and the use of a combination of chemotherapy with immunotherapy and hematopoietic stem cell transplantation for patients with risk factors. COMBINATION_PRODUCT

two-stage stratification into risk groups: Initially and According to the results of induction therapy MRD-positive patients receive a course of blinatumomab and HSCT.

intervention/treatment

Eligibility Criteria

• Age: 1 Day - 365 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age at diagnosis at 1 to 365 days of life.
• The start of induction therapy within a time interval of study recruitment phase.
• The diagnosis of ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow (see "Diagnostics"). Patients with B-cell (Burkitt) ALL are excluded.
• Informed consent of the patient parents (guardians) to be treated in one of the clinics included in this study.

You may not qualify if:

• The disease is a relapse of previously misdiagnosed and, therefore, inadequately treated ALL;
• There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.);
• There is a lack of important data needed for the exact adherence to the cytostatic therapy according to a specific chemotherapy protocol (differential diagnosis of ALL-AML (acute myeloid leukemia) is not possible, stratification according to therapeutic group is not possible);
• The patient was treated before for a long time with cytotoxic drugs;
• There were treatment deviations not covered by the protocol and/or not due to side effects of treatment and/or complications of the disease

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology

Moscow, Samory-Mashela,1, 11198, Russia

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy; Hematopoietic Stem Cell Transplantation; Risk Factors

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Transplantation; Surgical Procedures, Operative; Risk; Probability; Statistics as Topic; Epidemiologic Methods; Investigative Techniques; Causality; Epidemiologic Factors; Quality of Health Care; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Central Study Contacts

Natalya f Myakova, PD

CONTACT

+79035083576; Natalya.Myakova@fccho-moscow.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: August 31, 2021
• Study Start: September 23, 2021
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)