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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Bone Marrow Transplant Infection; Opportunistic Fungal Infection; Opportunistic Viral Infection
• Intervention / Treatment: Biological: Pentavalent-specific T cells (penta-STs)

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Evangelia Yannaki, MD; Phone Number: +302313307518; Email: eyannaki@uw.edu

Study Locations

• Greece
  • Patra, Greece
    • Recruiting
    • University General Hospital of Patras
    • Contact: Alexandros Spyridonidis, MD; Phone Number: +302613603506; Email: spyridonidis@upatras.gr
    • Contact: Alexandros Spyridonidis, MD; Email: spyridonidis@upatras.gr
  • Thessaloníki, Greece, 57010
    • Recruiting
    • George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
    • Contact: Evangelia Yannaki, MD; Phone Number: +302313307518; Email: eyannaki@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: George Papanicolaou Hospital
• Collaborators: University General Hospital of Patras
• Investigators: Principal Investigator: Evangelia Yannaki, MD, George Papanicolaou Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 24, 2022
• Primary Completion (ANTICIPATED): April 30, 2023
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: July 16, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (ACTUAL): July 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: BK virus; CMV; EBV; Adenovirus; Aspergillus Fumigatus
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Virus Diseases; Mycoses; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; PENTA
• Other Study ID Numbers: Penta-STs-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No