Clinical trial NCT05471661: T Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections After Allogeneic Stem Cell Transplantation
Official title: Administration of Rapidly Generated Multipathogen-specific T-Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections Post Allogeneic Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Opportunistic Fungal Infection
Opportunistic Viral Infection
Bone Marrow Transplant Infection
Keywords: CMV
EBV
BK virus
Adenovirus
Aspergillus Fumigatus
Lead sponsor: George Papanicolaou Hospital
Sponsor class: OTHER
Collaborators: name: University General Hospital of Patras
First posted: 2022-07-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients from Hematology Department- Hematopoietic Stem Cell Transplantation Unit, George Papanikolaou Hospital and Bone Marrow Transplantation Unit of the University Hospital of Patras will be eligible to receive penta-STs as treatment for infection of one or more of the target-pathogens or for increasing pathogen load in two consecutive timepoints, following any type of allogeneic transplant.

If patients are receiving steroids for treatment of GVHD or for other reasons, dosage must have been tapered to ≤0.5mg/kg prednisone (or equivalent) prior to study enrollment. Patients may not have received ATG, or Campath or other immunosuppressive monoclonal antibodies in the last 28 days.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute GvHD
timeFrame: Within 6 weeks post the last dose of penta-STs
measure: Chronic GvHD
timeFrame: Within 6 months post the last dose of penta-STs
measure: Infusion-related adverse events
timeFrame: Within 30 days of the last dose of penta-STs
measure: Non hematological, adverse events
timeFrame: Within 30 days of the last dose of penta-STs
measure: Resolution of infection - 1
timeFrame: 12 weeks post the last dose of penta-STs
measure: Resolution of infection - 2
timeFrame: 12 weeks post the last dose of penta-STs
measure: Antiviral immunity
timeFrame: 12 weeks post the last dose of penta-STs
measure: Antifungal immunity
timeFrame: 12 weeks post the last dose of penta-STs
measure: Viral reactivations or recurrence of AF infection
timeFrame: 6 months post the last dose of penta-STs
Secondary outcomes:
Other outcomes:
Locations:
city: Patra
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
Study officials:
affiliation: George Papanicolaou Hospital
name: Evangelia Yannaki, MD
role: PRINCIPAL_INVESTIGATOR
References: