Clinical trial NCT05066958: Ex-vivo Primed Memory Donor Lymphocyte Infusion to Boost Anti-viral Immunity After T-cell Depleted HSCT
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
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
Myelodysplastic Syndromes
Keywords: Hematopoietic stem cell transplantation
alpha/beta T cell depletion
CD45RA depletion
immune reconstitution
viral infections
ELISPOT
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2021-10-04
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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. 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).


Eligibility criteria: Inclusion Criteria:

1. Informed consent signed by the patient (ages 14 to 18) and / or his legal representative (ages 0 to 18).
2. The patient has an indication for allogeneic transplantation of hematopoietic stem cells established in accordance with the current regulatory framework
3. Planned HSCT selective immunomagnetic depletion of alpha/betta T lymphocytes
4. Karnovsky or Lansky index more than 50%
5. Life expectancy at least 4 weeks
6. Heart function: ejection fraction of at least 40%
7. Consent to continue follow-up for 5 years

Exclusion Criteria:

1. Acute viral hepatitis or acute HIV infection
2. Hypoxemia with SaO2 \<90%
3. Bilirubin\> 3 norms
4. Creatinine\> 3 norms
5. Pregnancy and lactation
6. Severe uncontrolled infection
7. Severe (\>?) pathology of the central nervous system (epilepsy, dementia, organic damage to the central nervous system, psychosis)

Primary outcomes:
measure: acute Graft Versus Host Disease
timeFrame: 100 days after HSCT
measure: The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to CMV
timeFrame: after HSCT by day + 30 and by day + 180
measure: The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to ADV
timeFrame: after HSCT by day + 30 and by day + 180
measure: The proportion of patients with detectable T-cell response (IFNgamma ELISPOT) to EBV
timeFrame: after HSCT by day + 30 and by day + 180
Secondary outcomes:
measure: Cumulative Incidence of developing chronic GVHD
timeFrame: after HSCT up to 2 years
measure: Cumulative Incidence of recurrence of leukemia CI of relapse
timeFrame: after HSCT up to 2 years
measure: TRM
timeFrame: after HSCT up to 2 years
measure: OS
timeFrame: after HSCT up to 2 years
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal Research Center for pediatric hematology, oncology and immunology
Study officials:
affiliation: Chief HSCT department at Federal Research Center for pediatric hematology, oncology and immunology
name: Mikchail m Maschan
role: STUDY_DIRECTOR
References: