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

Bone Marrow Transplant Infection Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05471661
• Other study ID #: Penta-STs-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 24, 2022
• Est. completion date: April 30, 2023

Study information

• Verified date: July 2022
• Source: George Papanicolaou Hospital
• Contact: Evangelia Yannaki, MD
• Phone: +302313307518
• Email: eyannaki[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: April 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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, ??V 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

Related Conditions & MeSH terms

• Bone Marrow Transplant Infection
• Communicable Diseases
• Infections
• Mycoses
• Virus Diseases

Intervention

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.

Locations

Country	Name	City	State
Greece	University General Hospital of Patras	Patra
Greece	George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center	Thessaloníki

Sponsors (2)

Lead Sponsor	Collaborator
George Papanicolaou Hospital	University General Hospital of Patras

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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