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

CMV Viremia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04018261
• Other study ID #: BST-LT-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 4, 2019
• Est. completion date: October 18, 2021

Study information

• Verified date: January 2024
• Source: Banc de Sang i Teixits
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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:

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: October 18, 2021
• Est. primary completion date: October 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• CMV Viremia
• Communicable Diseases
• Immunosuppression-related Infectious Disease
• Infections
• Viremia

Intervention

Drug:
• Activated T-Lymphocytes
Activated T-Lymphocytes will be infused intravenously in a single-dose

Locations

Country	Name	City	State
Spain	ICO Badalona	Badalona	Barcelona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Sant Joan de Déu	Esplugues De Llobregat	Barcelona
Spain	ICO l'Hospitalet	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario La Fe	Valencia

Sponsors (3)

Lead Sponsor	Collaborator
Banc de Sang i Teixits	Hospital Universitario La Fe, Vall d'Hebron Institute of Oncology

Country where clinical trial is conducted

Spain, 

Outcome

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

External Links

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