T Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections After Allogeneic Stem Cell Transplantation (Penta-STs-001)

General Hospital of Thessaloniki "George Papanikolaou"

Status and phase: Completed; Phase 2; Phase 1

Conditions: Bone Marrow Transplant Infection; Opportunistic Fungal Infection; Opportunistic Viral Infection

Treatments: Biological: Pentavalent-specific T cells (penta-STs)

Study type: Interventional

Funder types: Other

Identifiers

NCT05471661

Penta-STs-001

Details and patient eligibility

About

The purpose of the study is to determine the feasibility, safety and efficacy of administering rapidly-generated donor-derived pentavalent-specific T cells (Penta-STs) to mediate antiviral and antifungal activity in hematopoietic stem cell transplant (HSCT) recipients with AdV, EBV, CMV, BKV or Aspergillus fumigatus (AF) infection/ reactivation or with active disease.

Full description

Reconstitution of anti-viral and antifungal immunity by donor-derived antigen-specific T cells has shown promise in preventing and treating infections with CMV, or/and EBV, or/and AdV or/and BKV, HHV6 or/and AF post-transplant. However, the broader implementation of T cell immunotherapy using conventional protocols is limited and until today it was practically impossible for Greece by the cost, the complexity and the time required for virus-specific T cells (VSTs) production and by the antigenic competition between different antigens, which limits the spectrum of viruses that can be targeted in a single T cell product.

In this trial, the investigators will evaluate the feasibility, safety and efficacy of donor-derived Penta-STs infusion to allogeneic HSCT recipients with confirmed AdV, EBV, CMV, BKV and AF infection.

Enrollment: 10 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Received prior myeoloablative or nonmyeloablative allogeneic hematopoietic stem cell transplant.
2. Cells administered as treatment for single or multiple infections/reactivations of one or more of the following pathogens: AdV, CMV, EBV, ΒΚV and AF.
3. Karnofsky/Lansky score of ≥ 50.
4. ANC > 500/μl.
5. Bilirubin ≤ 2x*, AST < 3x*, Serum creatinine ≤ 2x*, Hemoglobin > 8.0 g/dl.
6. Pulse oximetry of > 90% on room air.
7. Available pentavalent-specific T cells.
8. Negative pregnancy test (if female of childbearing potential)
9. Patient capable of providing informed consent.

Exclusion criteria

1. Received ATG, or Campath or other T cell immunosuppressive monoclonal antibodies in the last 28 days.
2. Steroids > 0.5 mg/kg/day prednisone.
3. Received donor lymphocyte infusion in last 28 days.
4. GVHD ≥ grade 2.
5. Active and uncontrolled relapse of malignancy.
6. Patients with other uncontrolled infections

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Penta-STs

Experimental group

Description:

Patients will receive penta-STs in a single infusion. If they have a partial response or receive therapy post-infusion which could ablate the infused T cells they are eligible to receive up to 2 additional doses from 28 days after their first dose.

Treatment:

Biological: Pentavalent-specific T cells (penta-STs)