Acute Lymphoblastic Leukemia, PediatricPhase 3NCT05029531
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 study testing 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 people with Acute Lymphoblastic Leukemia, Pediatric and ALL, Infants, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 365 days
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Pediatric, ALL, Infants
- What is being tested?
- 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.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteRussia
- Study dates
- 23 Sep 2021to 1 Jul 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 365 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
Moscow, Samory-Mashela,1, 11198
Lena f Smirnova, lena.smirnova@fccho-moscow.ru
About this study
Official title: Prospective Single Group Study Combined Immuno-hemotherapy for Patients With B-linear Acute Lymphoblastic Leukemia Diagnosed From 0 to 365 Days of Life (ALL-Baby-2021)
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:
Read more
- 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).
- Being tested
- 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.
- Keywords
- Acute lymphoblastic leukemia, children, infant, treatment сhemotherapy, Immunotherapy, Blinatumomab, Stemm Cell Transplantation
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| intervention/treatment | Experimental | Not described Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
event free survival
Measured: 4 years after the start of therapy
overal survival
Measured: 4 years after the start of therapy
Secondary outcomes (4)
risk of relapse
survival analysis, cumulative risks
Measured: 3 years after the start of therapy
frequency of achieving MRD-negative remission
Measured: after a course of induction up to 1 week
frequency of achieving MRD-negative remission
Measured: after a course of consolidation up to 1 week
mortality associated with HSCT
survival analysis, cumulative risks
Measured: 2 years post HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2021
- Study start23 Sep 2021
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia, PediatricStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05029531
- Sponsor's protocol ID
- NCHPOI-2021-03
- Status last verified
- Jun 2024
- First submitted
- 26 Aug 2021
- Last updated
- 28 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Single Group Study Combined Immuno-hemotherapy for Patients With B-linear Acute Lymphoblastic Leukemia Diagnosed From 0 to 365 Days of Life (ALL-Baby-2021)
- ClinicalTrials.gov ID
- NCT05029531
- Acronym / sponsor ID
- NCHPOI-2021-03
- Keywords
- Acute lymphoblastic leukemia, children, infant, treatment сhemotherapy, Immunotherapy, Blinatumomab, Stemm Cell Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2030 (estimated)
- First posted
- 31 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 1 day to 365 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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.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. | Combination product | intervention/treatment |
Primary outcome
event free survival
Time frame: 4 years after the start of therapy
overal survival
Time frame: 4 years after the start of therapy
4 secondary outcomes
risk of relapse
Time frame: 3 years after the start of therapy
frequency of achieving MRD-negative remission
Time frame: after a course of induction up to 1 week
frequency of achieving MRD-negative remission
Time frame: after a course of consolidation up to 1 week
mortality associated with HSCT
Time frame: 2 years post HSCT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 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 people with Acute Lymphoblastic Leukemia, Pediatric and ALL, Infants, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natalya f Myakova, PD (+79035083576, Natalya.Myakova@fccho-moscow.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
event free survival (time frame: 4 years after the start of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024.