Acute Myeloid LeukemiaPhase 1/2NCT05066958
Ex-vivo Primed Memory Donor Lymphocyte Infusion to Boost Anti-viral Immunity After T-cell Depleted HSCT
A Phase 1/2 study testing boost anti-viral immunity after T-cell depleted HSCT in people with Acute Myeloid Leukemia and High Risk Acute Myeloid Leukemia, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
HSCT from an allogeneic donor is the standard therapy for high-risk hematopoietic malignancies and a wide range of severe non-malignant diseases of the blood and immune system. The possibility of performing HSCT was significantly limited by the availability of donors compatible with the MHC system. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Acute Myeloid Leukemia, High Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, in Relapse
- What is being tested?
- boost anti-viral immunity after T-cell depleted HSCT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteRussia
- Study dates
- 16 Sep 2021to 1 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Informed consent signed by the patient (ages 14 to 18) and / or his legal representative (ages 0 to 18).
- The patient has an indication for allogeneic transplantation of hematopoietic stem cells established in accordance with the current regulatory framework
- Planned HSCT selective immunomagnetic depletion of alpha/betta T lymphocytes
- Karnovsky or Lansky index more than 50%
- Life expectancy at least 4 weeks
- Heart function: ejection fraction of at least 40%
- Consent to continue follow-up for 5 years
Who cannot join
- Acute viral hepatitis or acute HIV infection
- Hypoxemia with SaO2 <90%
- Bilirubin> 3 norms
- Creatinine> 3 norms
- Pregnancy and lactation
- Severe uncontrolled infection
- Severe (>?) pathology of the central nervous system (epilepsy, dementia, organic damage to the central nervous system, psychosis)
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Federal Research Center for pediatric hematology, oncology and immunology
Moscow, 117997
Michael Maschan, MD, 007 916 651 21 45, mmaschan@yandex.ru
About this study
Official title: Safety and Efficacy Study of an Ex-vivo Antigen-primed Donor Memory Lymphocyte Infusion for the Enhancement of Immunity to Viral Infections Among Recipients of Allogeneic Hematopoietic Stem Cell Transplantation on the Platform of Selective Immunomagnetic Depletion of T-lymphocytes
HSCT from an allogeneic donor is the standard therapy for high-risk hematopoietic malignancies and a wide range of severe non-malignant diseases of the blood and immune system. The possibility of performing HSCT was significantly limited by the availability of donors compatible with the MHC system. However, modern ex-vivo and in vivo technologies for depletion of T lymphocytes have made it possible to improve the outcomes of HSCT from partially compatible related (haploidentical) donors. In representative groups, it was shown that the success of HSCT from haploidentical donors is not inferior to standard procedures of HSCT from HLA-compatible unrelated donors. HSCT from haploidentical donors in children associated with the deficit of the adaptive immune response, which persists up to 6 months after HSCT and can be an increased risk of death of the patient from opportunistic infections. To solve this problem, the method of infusion of low doses of donor memory T lymphocytes was introduced. This technology is based on the possibility of adoptive transfer of memory immune response to key viral pathogens from donor to recipient. Such infusions have been shown to be safe and to accelerate the recovery of the pathogen-specific immune response. The expansion of virus-specific T lymphocytes in the recipient's body depends on exposure to the relevant antigen in vivo. Thus, in the absence of contact with the viral antigen, the adoptive transfer of memory T lymphocytes is not accompanied in vivo by the expansion of virus-specific lymphocytes and does not form a circulating pool of memory T lymphocytes, that can protect the patient from infections. Therefore the investigators assume that ex-vivo priming of donor memory lymphocytes with relevant antigens can provide optimal antigenic stimulation and may solve the problem of restoring immunological reactivity in the early stages after HSCT. Technically ex-vivo primed memory T lymphocytes will be generated by short incubation of CD45RA-depleted fraction of the graft (a product of T lymphocyte depletion) with a pool of GMP-quality peptides representing a number of key proteins of the viral pathogens. The following are proposed as targeted antigens: CMV pp65, EBV EBNA-1, EBV LMP12A, Adeno AdV5 Hexon, BKV LT, BKV VP1. An infusion of donor memory lymphocytes will be performed on the day +1 after transplantation. Parameters of the assessment will be safety and efficacy (immune response by day 60 and stability (responses by day 180).
- Conditions
- Acute Myeloid Leukemia, High Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, in Relapse, High Risk Acute Lymphoblastic Leukemia, Acute Biphenotypic Leukemia in Relapse, Non-hodgkin Lymphoma
- Being tested
- boost anti-viral immunity after T-cell depleted HSCT
- Keywords
- Hematopoietic stem cell transplantation, alpha/beta T cell depletion, CD45RA depletion, immune reconstitution, viral infections, ELISPOT
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
boost anti-viral immunity after T-cell depleted HSCTBiological
- Registration and informed consent sign
- Screening clinical and laboratory examination, assessment of compliance with inclusion criteria
- Survey of the recipient and potential donors
- Donor selection
- The study of the immune response to relevant antigens in the donor and recipient
- Pre-transplant conditioning
- Stimulation of the donor and apheresis of peripheral blood mononuclear cells
- Graft processing
- The manufacturing of cell product
- Transplant Infusion
- Antigen-primed memory DLI infusion
- Inpatient care until day +30
- Outpatient monitoring and screening
| Study group | Role | What they receive |
|---|---|---|
| boost anti-viral immunity after T-cell depleted HSCT | Experimental | Not described Receives: Biological: boost anti-viral immunity after T-cell depleted HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
acute Graft Versus Host Disease
Cumulative risk of developing of acute Graft Versus Host Disease (aGVHD) (evaluation period is 100 days) stage II-IV
Measured: 100 days after HSCT
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to CMV
The proportion of patients with detectable peripheral blood T-lymphocytes specific for CMV antigens
Measured: after HSCT by day + 30 and by day + 180
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to ADV
The proportion of patients with detectable peripheral blood T-lymphocytes specific for ADV antigens
Measured: after HSCT by day + 30 and by day + 180
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to EBV
The proportion of patients with detectable peripheral blood T-lymphocytes specific for EBV antigens
Measured: after HSCT by day + 30 and by day + 180
Secondary outcomes (4)
Cumulative Incidence of developing chronic GVHD
Cumulative Incidence of developing chronic GVHD
Measured: after HSCT up to 2 years
Cumulative Incidence of recurrence of leukemia CI of relapse
Cumulative Incidence of recurrence of leukemia
Measured: after HSCT up to 2 years
TRM
Cumulative Incidence of transplant-related mortality
Measured: after HSCT up to 2 years
OS
Overall survival
Measured: after HSCT up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start16 Sep 2021
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- Investigators
- Mikchail m Maschan, Study director, Chief HSCT department at Federal Research Center for pediatric hematology, oncology and immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05066958
- Sponsor's protocol ID
- NCPHOI-2020-06
- Status last verified
- Sep 2021
- First submitted
- 22 Sep 2021
- Last updated
- 4 Oct 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Study of an Ex-vivo Antigen-primed Donor Memory Lymphocyte Infusion for the Enhancement of Immunity to Viral Infections Among Recipients of Allogeneic Hematopoietic Stem Cell Transplantation on the Platform of Selective Immunomagnetic Depletion of T-lymphocytes
- ClinicalTrials.gov ID
- NCT05066958
- Acronym / sponsor ID
- NCPHOI-2020-06
- Conditions
- Acute Myeloid Leukemia, High Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, in Relapse, High Risk Acute Lymphoblastic Leukemia, Acute Biphenotypic Leukemia in Relapse, Non-hodgkin Lymphoma
- Keywords
- Hematopoietic stem cell transplantation, alpha/beta T cell depletion, CD45RA depletion, immune reconstitution, viral infections, ELISPOT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 16 Sep 2021 (actual)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 4 Oct 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.
HSCT from an allogeneic donor is the standard therapy for high-risk hematopoietic malignancies and a wide range of severe non-malignant diseases of the blood and immune system. The possibility of performing HSCT was significantly limited by the availability of donors compatible with the MHC system. However, modern ex-vivo and in vivo technologies for depletion of T lymphocytes have made it possible to improve the outcomes of HSCT from partially compatible related (haploidentical) donors. In representative groups, it was shown that the success of HSCT from haploidentical donors is not inferior to standard procedures of HSCT from HLA-compatible unrelated donors. HSCT from haploidentical donors in children associated with the deficit of the adaptive immune response, which persists up to 6 months after HSCT and can be an increased risk of death of the patient from opportunistic infections. To solve this problem, the method of infusion of low doses of donor memory T lymphocytes was introduced. This technology is based on the possibility of adoptive transfer of memory immune response to key viral pathogens from donor to recipient. Such infusions have been shown to be safe and to accelerate the recovery of the pathogen-specific immune response. The expansion of virus-specific T lymphocytes in the recipient's body depends on exposure to the relevant antigen in vivo. Thus, in the absence of contact with the viral antigen, the adoptive transfer of memory T lymphocytes is not accompanied in vivo by the expansion of virus-specific lymphocytes and does not form a circulating pool of memory T lymphocytes, that can protect the patient from infections. Therefore the investigators assume that ex-vivo priming of donor memory lymphocytes with relevant antigens can provide optimal antigenic stimulation and may solve the problem of restoring immunological reactivity in the early stages after HSCT. Technically ex-vivo primed memory T lymphocytes will be generated by short incubation of CD45RA-depleted fraction of the graft (a product of T lymphocyte depletion) with a pool of GMP-quality peptides representing a number of key proteins of the viral pathogens. The following are proposed as targeted antigens: CMV pp65, EBV EBNA-1, EBV LMP12A, Adeno AdV5 Hexon, BKV LT, BKV VP1. An infusion of donor memory lymphocytes will be performed on the day +1 after transplantation. Parameters of the assessment will be safety and efficacy (immune response by day 60 and stability (responses by day 180).
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| boost anti-viral immunity after T-cell depleted HSCT | Experimental | Biological: boost anti-viral immunity after T-cell depleted HSCT |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Informed consent signed by the patient (ages 14 to 18) and / or his legal representative (ages 0 to 18).
- The patient has an indication for allogeneic transplantation of hematopoietic stem cells established in accordance with the current regulatory framework
- Planned HSCT selective immunomagnetic depletion of alpha/betta T lymphocytes
- Karnovsky or Lansky index more than 50%
- Life expectancy at least 4 weeks
Key exclusion criteria (7 listed)
- Acute viral hepatitis or acute HIV infection
- Hypoxemia with SaO2 <90%
- Bilirubin> 3 norms
- Creatinine> 3 norms
- Pregnancy and lactation
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 |
|---|---|---|
| boost anti-viral immunity after T-cell depleted HSCT* Registration and informed consent sign * Screening clinical and laboratory examination, assessment of compliance with inclusion criteria * Survey of the recipient and potential donors * Donor selection * The study of the immune response to relevant antigens in the donor and recipient * Pre-transplant conditioning * Stimulation of the donor and apheresis of peripheral blood mononuclear cells * Graft processing * The manufacturing of cell product * Transplant Infusion * Antigen-primed memory DLI infusion * Inpatient care until day +30 * Outpatient monitoring and screening | Biological | boost anti-viral immunity after T-cell depleted HSCT |
Primary outcome
acute Graft Versus Host Disease
Time frame: 100 days after HSCT
Cumulative risk of developing of acute Graft Versus Host Disease (aGVHD) (evaluation period is 100 days) stage II-IV
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to CMV
Time frame: after HSCT by day + 30 and by day + 180
The proportion of patients with detectable peripheral blood T-lymphocytes specific for CMV antigens
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to ADV
Time frame: after HSCT by day + 30 and by day + 180
The proportion of patients with detectable peripheral blood T-lymphocytes specific for ADV antigens
The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to EBV
Time frame: after HSCT by day + 30 and by day + 180
The proportion of patients with detectable peripheral blood T-lymphocytes specific for EBV antigens
4 secondary outcomes
Cumulative Incidence of developing chronic GVHD
Time frame: after HSCT up to 2 years
Cumulative Incidence of recurrence of leukemia CI of relapse
Time frame: after HSCT up to 2 years
TRM
Time frame: after HSCT up to 2 years
OS
Time frame: after HSCT up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
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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. This study is not recruiting at the moment.
Mikchail m Maschan study director
Chief HSCT department at Federal Research Center for pediatric hematology, oncology and immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing boost anti-viral immunity after T-cell depleted HSCT in people with Acute Myeloid Leukemia and High Risk Acute Myeloid Leukemia, 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 7 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 4 Oct 2021. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michail m Maschan, PD (+7 (495)2876570, mmaschan@yandex.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
acute Graft Versus Host Disease (time frame: 100 days after HSCT). The study lists 4 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 4 Oct 2021.