T Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections After Allogeneic Stem Cell Transplantation

Phase 1

Completed

• Conditions: Opportunistic Viral Infection; Bone Marrow Transplant Infection; Opportunistic Fungal Infection
• Interventions: Biological: Pentavalent-specific T cells (penta-STs)

• Registration Number: NCT05471661
• Lead Sponsor: George Papanicolaou Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-05-22
• Study First Submitted: 2022-07-16
• Study First Submitted QC: 2022-07-20
• Study First Posted: 2022-07-25
• Primary Completion: 2024-05-05
• Study Completion: 2024-05-08
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-24
• Last Update Posted: 2024-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Penta-STs	Pentavalent-specific T cells (penta-STs)	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.

Primary Outcome Measures

Name	Time	Method
Acute GvHD	Within 6 weeks post the last dose of penta-STs	The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Chronic GvHD	Within 6 months post the last dose of penta-STs	The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Infusion-related adverse events	Within 30 days of the last dose of penta-STs	The safety of cell therapy with penta-STs will be assessed according to grades ≥3 infusion-related adverse events
Non hematological, adverse events	Within 30 days of the last dose of penta-STs	The safety of cell therapy with penta-STs will be assessed according to grades ≥3 non hematological, adverse events within 30 days of the last penta-ST dose, which are not due to the preexisting infection/comorbidities or the original malignancy
Resolution of infection - 1	12 weeks post the last dose of penta-STs	The efficacy of penta-STs will be determined based on the reduction/elimination of pathogen load in patients with infections
Resolution of infection - 2	12 weeks post the last dose of penta-STs	The efficacy of penta-STs will be determined based on the amelioration/elimination of clinical symptoms in patients with viral disease
Antiviral immunity	12 weeks post the last dose of penta-STs	The efficacy of penta-STs will be determined based on the reconstitution of antiviral immunity (determination of virus-specific T cells)
Antifungal immunity	12 weeks post the last dose of penta-STs	The efficacy of penta-STs will be determined based on reconstitution of antifungal immunity (determination of Aspergillus fumigatus-specific T cells)
Viral reactivations or recurrence of AF infection	6 months post the last dose of penta-STs	The efficacy of penta-STs will be determined by the absence of viral reactivations or recurrence of AF infection post penta-STs infusion

Trial Locations

Locations (2)

University General Hospital of Patras; 🇬🇷 Patra, Greece

George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center; 🇬🇷 Thessaloníki, Greece