Ex-vivo Primed Memory Donor Lymphocyte Infusion to Boost Anti-viral Immunity After T-cell Depleted HSCT

NCT ID: NCT05066958

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-16
• Study Completion Date: 2022-12-01

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).

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

boost anti-viral immunity after T-cell depleted HSCT

Group Type: EXPERIMENTAL

boost anti-viral immunity after T-cell depleted HSCT

Intervention Type: BIOLOGICAL

• 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

Interventions

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

Intervention Type: BIOLOGICAL

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)

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikchail m Maschan

Role: STUDY_DIRECTOR

Chief HSCT department at Federal Research Center for pediatric hematology, oncology and immunology

Locations

Federal Research Center for pediatric hematology, oncology and immunology

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Michail m Maschan, PD

Role: CONTACT

mmaschan@yandex.ru

+7 (495)2876570

Facility Contacts

Michael Maschan, MD

Role: primary

mmaschan@yandex.ru

007 916 651 21 45

Other Identifiers

NCPHOI-2020-06

Identifier Type: -

Identifier Source: org_study_id