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RecruitingNCT05029531Updated Jun 28, 2024

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

A Phase 3 interventional study of 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. in Acute Lymphoblastic Leukemia, Pediatric and ALL, Infants, sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology. Recruiting at 1 site in Russian Federation. Open to participants aged 1 Day to 365 Days. Per ClinicalTrials.gov, last updated 2024-06-28.

Sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
80
Allocation
Not applicable
Ages
1 Day to 365 Days
Sex
All
01

Study 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.
Read the detailed description
  • Standard risk group:
  • Induction of remission: 36 days of dexamethasone, 5 weekly injections of vincristine, 2 injections of daunorubicin on days 8 and 22, a single injection of pegelated asparaginase on days 5-7 and 6 weekly intrathecal injections of three drugs (methotrexate, cyamethosar and dexamethason ).
  • Further therapy in this therapeutic group depends on the status of remission, the level of MRD on the 36th day of therapy.
  • MRD-negative patients receive consolidation therapy in the amount of 3 consolidations (6-mercaptopurine, methotrexate, peg-asparaginase, daunorubicin) with re-induction courses (dexamethasone, vincristine) and maintenance therapy (6-mercaptopurine, methotrexate).
  • MRD-positive patients receive a course of blinatumomab and HSCT.
  • Intermediate risk group:
  • Induction of remission: 36 days of dexamethasone, 5 weekly injections of vincristine, 2 injections of daunorubicin on days 8 and 22, a single injection of pegelated asparaginase on days 5-7, 6 weekly intrathecal injections of three drugs (methotrexate, cyamethosar, dexamethasone).
  • Further therapy in this therapeutic group depends on the status of remission on the 36th day of therapy.
  • Patients who have achieved molecular remission receive consolidation therapy in the amount of 3 consolidations with re-induction courses and maintenance therapy.
  • Patients who have not achieved molecular remission receive HR1 block. Further therapy depends on the remission status after HR1 block. Patients who have not achieved molecular remission receive a course of blinatumomab and HSCT, patients who have achieved molecular remission, two more blocks HR2 and HR3, protocol II and maintenance therapy.
  • High risk group:
  • Induction of remission: 36 days of dexamethasone, 5 weekly injections of vincristine, 2 injections of daunorubicin on days 8 and 22, a single injection of pegelated asparaginase on days 5-7, 6 weekly intrathecal injections of three drugs (methotrexate, cyamethosar, dexamethasone).
  • Further therapy in this therapeutic group does not depend on the status of remission on the 36th day of therapy.
  • All patients receive HR1 block, blinatumomab course and HSCT (subject to morphological remission).
02

Conditions studied

  • Acute Lymphoblastic Leukemia, Pediatric
  • ALL, Infants

Keywords

  • Acute lymphoblastic leukemia
  • children
  • infant
  • treatment сhemotherapy
  • Immunotherapy
  • Blinatumomab
  • Stemm Cell Transplantation
03

Who can participate

Ages eligible
1 Day to 365 Days
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
80 participants (estimated)

Study arms

  • Experimental
    intervention/treatment

    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

  • Combination productthe 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.

    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.

05

What researchers measure

Primary outcomes

  1. event free survival

    Time frame: 4 years after the start of therapy

  2. overal survival

    Time frame: 4 years after the start of therapy

Secondary outcomes

  1. risk of relapse

    survival analysis, cumulative risks

    Time frame: 3 years after the start of therapy

  2. frequency of achieving MRD-negative remission

    Time frame: after a course of induction up to 1 week

  3. frequency of achieving MRD-negative remission

    Time frame: after a course of consolidation up to 1 week

  4. mortality associated with HSCT

    survival analysis, cumulative risks

    Time frame: 2 years post HSCT

06

Study locations

1 of 1 sites recruiting
  • Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
    Moscow, Samory-Mashela,1 11198, Russian Federation
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05029531
Lead sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Responsible party
Sponsor
First posted
Aug 31, 2021
Start date
Sep 23, 2021
Primary completion
Jul 1, 2029 (estimated)
Completion
Jul 1, 2030 (estimated)
Last update
Jun 28, 2024

Study contacts

Natalya f Myakova, PD
Contact
Natalya.Myakova@fccho-moscow.ru
+79035083576

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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