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

NCT05471661 | Completed Phase 1 DMC

• 1 other identifier: Penta-STs-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

CMV; EBV; BK virus; Adenovirus; Aspergillus Fumigatus

Outcome Measures

Primary Outcomes (9)

• Acute GvHD

  The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV

  Within 6 weeks post the last dose of penta-STs

• Chronic GvHD

  The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV

  Within 6 months post the last dose of penta-STs

• Infusion-related adverse events

  The safety of cell therapy with penta-STs will be assessed according to grades ≥3 infusion-related adverse events

  Within 30 days of the last dose of penta-STs

• Non hematological, adverse events

  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

  Within 30 days of the last dose of penta-STs

• Resolution of infection - 1

  The efficacy of penta-STs will be determined based on the reduction/elimination of pathogen load in patients with infections

  12 weeks post the last dose of penta-STs

• Resolution of infection - 2

  The efficacy of penta-STs will be determined based on the amelioration/elimination of clinical symptoms in patients with viral disease

  12 weeks post the last dose of penta-STs

• Antiviral immunity

  The efficacy of penta-STs will be determined based on the reconstitution of antiviral immunity (determination of virus-specific T cells)

  12 weeks post the last dose of penta-STs

• Antifungal immunity

  The efficacy of penta-STs will be determined based on reconstitution of antifungal immunity (determination of Aspergillus fumigatus-specific T cells)

  12 weeks post the last dose of penta-STs

• Viral reactivations or recurrence of AF infection

  The efficacy of penta-STs will be determined by the absence of viral reactivations or recurrence of AF infection post penta-STs infusion

  6 months post the last dose of penta-STs

Study Arms (1)

Penta-STs

EXPERIMENTAL

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.

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

Interventions

Pentavalent-specific T cells (penta-STs) BIOLOGICAL

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.

Penta-STs

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• George Papanicolaou Hospital: lead
• University General Hospital of Patras: collaborator

Study Sites (2)

University General Hospital of Patras

Pátrai, Greece

Location

George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center

Thessaloniki, 57010, Greece

Location

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Evangelia Yannaki, MD

  George Papanicolaou Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI, Director of the Gene and Cell Therapy Center, Hematology-HCT Unit

Model Details: 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.

Study Record Dates

• First Submitted: July 16, 2022
• First Posted: July 25, 2022
• Study Start: May 22, 2021
• Primary Completion: May 5, 2024
• Study Completion: May 8, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2)