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

Primary Purpose

Opportunistic Fungal Infection, Opportunistic Viral Infection, Bone Marrow Transplant Infection

Status
Recruiting
Phase
Phase 1
Locations
Greece
Study Type
Interventional
Intervention
Pentavalent-specific T cells (penta-STs)
Sponsored by
George Papanicolaou Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opportunistic Fungal Infection focused on measuring CMV, EBV, BK virus, Adenovirus, Aspergillus Fumigatus

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts 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

Sites / Locations

  • University General Hospital of PatrasRecruiting
  • George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Penta-STs

Arm 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.

Outcomes

Primary Outcome Measures

Acute GvHD
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Chronic GvHD
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Infusion-related adverse events
The safety of cell therapy with penta-STs will be assessed according to grades ≥3 infusion-related adverse events
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
Resolution of infection - 1
The efficacy of penta-STs will be determined based on the reduction/elimination of pathogen load in patients with infections
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
Antiviral immunity
The efficacy of penta-STs will be determined based on the reconstitution of antiviral immunity (determination of virus-specific T cells)
Antifungal immunity
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
The efficacy of penta-STs will be determined by the absence of viral reactivations or recurrence of AF infection post penta-STs infusion

Secondary Outcome Measures

Full Information

First Posted
July 16, 2022
Last Updated
July 26, 2022
Sponsor
George Papanicolaou Hospital
Collaborators
University General Hospital of Patras
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1. Study Identification

Unique Protocol Identification Number
NCT05471661
Brief Title
T Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections After Allogeneic Stem Cell Transplantation
Acronym
Penta-STs-001
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
George Papanicolaou Hospital
Collaborators
University General Hospital of Patras

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opportunistic Fungal Infection, Opportunistic Viral Infection, Bone Marrow Transplant Infection
Keywords
CMV, EBV, BK virus, Adenovirus, Aspergillus Fumigatus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Penta-STs
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Pentavalent-specific T cells (penta-STs)
Intervention 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.
Primary Outcome Measure Information:
Title
Acute GvHD
Description
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Time Frame
Within 6 weeks post the last dose of penta-STs
Title
Chronic GvHD
Description
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Time Frame
Within 6 months post the last dose of penta-STs
Title
Infusion-related adverse events
Description
The safety of cell therapy with penta-STs will be assessed according to grades ≥3 infusion-related adverse events
Time Frame
Within 30 days of the last dose of penta-STs
Title
Non hematological, adverse events
Description
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
Time Frame
Within 30 days of the last dose of penta-STs
Title
Resolution of infection - 1
Description
The efficacy of penta-STs will be determined based on the reduction/elimination of pathogen load in patients with infections
Time Frame
12 weeks post the last dose of penta-STs
Title
Resolution of infection - 2
Description
The efficacy of penta-STs will be determined based on the amelioration/elimination of clinical symptoms in patients with viral disease
Time Frame
12 weeks post the last dose of penta-STs
Title
Antiviral immunity
Description
The efficacy of penta-STs will be determined based on the reconstitution of antiviral immunity (determination of virus-specific T cells)
Time Frame
12 weeks post the last dose of penta-STs
Title
Antifungal immunity
Description
The efficacy of penta-STs will be determined based on reconstitution of antifungal immunity (determination of Aspergillus fumigatus-specific T cells)
Time Frame
12 weeks post the last dose of penta-STs
Title
Viral reactivations or recurrence of AF infection
Description
The efficacy of penta-STs will be determined by the absence of viral reactivations or recurrence of AF infection post penta-STs infusion
Time Frame
6 months post the last dose of penta-STs

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Evangelia Yannaki, MD
Phone
+302313307518
Email
eyannaki@uw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evangelia Yannaki, MD
Organizational Affiliation
George Papanicolaou Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University General Hospital of Patras
City
Patra
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandros Spyridonidis, MD
Phone
+302613603506
Email
spyridonidis@upatras.gr
First Name & Middle Initial & Last Name & Degree
Alexandros Spyridonidis, MD
Email
spyridonidis@upatras.gr
Facility Name
George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
City
Thessaloníki
ZIP/Postal Code
57010
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Evangelia Yannaki, MD
Phone
+302313307518
Email
eyannaki@uw.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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