Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients

A Prospective Multicenter Open-label, Not Controlled Phase Ib-II Clinical Trial to Assess the Safety and Immunologic Efficacy of Virus-specific T Lymphocytes From the Best Donor in Receptors of Hematopoietic Progenitor Allogeneic Transplant

Marrow transplanted immunocompromised patients with cytomegalovirus (CMV) viral infection will be treated with CMV activated T-Lymphocytes. T-Lymphocytes will be obtained through an apheresis from a compatible donor.

Safety and immunoreconstitution parameters in blood samples will be assessed up to +60 days after the treatment.

Study Overview

• Status: Completed
• Conditions: CMV Viremia; Immunosuppression-related Infectious Disease
• Intervention / Treatment: Drug: Activated T-Lymphocytes

Detailed Description

A prospective, multicentre, open-label and uncontrolled phase Ib-II clinical trial in which a total of 20 patients ≥ 1 year of age with an allogeneic transplant of hematopoietic progenitors and post-transplant CMV infection will be included. The main objective is to evaluate the safety of the infusion of CMV activated T-lymphocytes and secondary objectives are to evaluate the efficacy through clinical evolution, viral load, ability to induce immunoreconstitution against the virus and evaluation of the persistence of specific T cells.

The treatment will be administered intravenously (central or peripheral route) in a single dose at a dose of 0.01-5 E4 specific virus T lymphocytes per Kg of receptor weight. After the infusion, patients will follow periodic controls (+7, +14, +21, +28, +45 and +60 days) in which a clinical evaluation will be performed and blood samples will be obtained in order to evaluate the persistence of specific T cells in the recipient:

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall D'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • ICO Badalona
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO l'Hospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Recipient of an allogeneic hematopoietic progenitors cell transplant (irrespectively of the donor source, donor type conditioning and underlying disease) that is beyond the day +30 of the procedure

2. Patient with post-transplant infection due to CMV refractory or resistant to optimal pharmacological treatment. Specifically, the patient must be included in any of the following cases

   1. Patient with organic disease caused by CMV (confirmed by histology) resistant to antiviral first line treatment
   2. Patient with CMV reactivation and no organic disease, resistant or intolerant to 2 previous antiviral treatment lines (ganciclovir/valganciclovir and foscarnet) or not candidate to be treated due to not acceptable expected toxicity (severe renal insufficiency, neutropenia or severe thrombopenia) It is agreed that the patient is affected with a resistant CMV infection if the CMV copies doesn't decrease in > 1 log in total blood or otherwise the absolute number of copies > 1x10E4/mL in total blood after 2 weeks of antiviral treatment.
   3. Patients with reactivation of recurrent CMV despite correct anti-CMV treatment. It will be considered a recurrent CMV infection if the patient has > 2 reactivations in a period <6 months despite having received correct anti-CMV treatment
   4. Documented genetic mutations associated with ganciclovir or foscarnet resistance
3. ≥ 1 year of age
4. Estimated life expectancy > 30 days
5. Signature of the informed consent form

Exclusion Criteria:

1. Acute graft-versus-host disease (GVHD) ≥ grade II or chronic ≥ moderate
2. Corticosteroid ≥ 0.5mg/kg regardless the indication
3. Disease relapse at the time of infection or at any time after the Allogeneic transplant.
4. Severe renal disease (creatinine > 3gr/dL)
5. Severe hepatic disease (bilirubin >3mg/dL or aspartate aminotransferase (AST) >500 U/L) except if it is secondary to the viral infection.
6. Having received a donor lymphocytes infusion or any cell therapy product within 60 days prior to inclusion in the study (with the exception of transfusions), or having it planned within the next 60 days.
7. Alteration of the general condition, infection or clinical or hemodynamic instability that, in the opinion of the researcher, does not recommend the use of T cells
8. Known hypersensitivity to murine proteins or iron dextran.
9. Positive serology to human immunodeficiency virus (HIV), hepatitis B virus (HBV) (HBsAg, HBcAc), hepatitis C virus (HCV) and/or syphilis
10. Pregnant, lactating or women without adequate contraception
11. Participation in a clinical trial with investigational medicinal products the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Activated T-Lymphocytes; Allogeneic T-Lymphocytes obtained from apheresis activated against CMV.	Drug: Activated T-Lymphocytes; Activated T-Lymphocytes will be infused intravenously in a single-dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment: Adverse events	Adverse events	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymerase chain reaction (PCR)	Quantitative viral load	+7, +14, +21, +28, +45, +60 days
IFN-γ+ spot forming cells	Immune reconstitution by Elispot	+7, +14, +28, +60 days
Lymphocyte subpopulations	Immune reconstitution by flow cytometry	+7, +14, +28, +60 days
T-cell persistence by chimerism	Detection of donor cellularity (administered product) in the receptor serum	+14, +28 days
Time elapsed in identifying the donor	Time elapsed between the patient's inclusion in the trial and confirmation of the donor	Day 0

Collaborators and Investigators

• Sponsor: Banc de Sang i Teixits
• Collaborators: Hospital Universitario La Fe; Vall d'Hebron Institute of Oncology
• Investigators: Principal Investigator: Pere Barba, MD, PhD, VHIO (Vall d'Hebron Institute of Oncology)

Publications and helpful links

Helpful Links

• Blood and Tissue Bank of Catalonia
• Vall d'Hebron Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Actual): October 18, 2021
• Study Completion (Actual): October 18, 2021

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppression; Cell therapy; CMV; Bone marrow transplant; Activated T-Lymphocytes; Virus infection
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Infections; Communicable Diseases; Viremia
• Other Study ID Numbers: BST-LT-01

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