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

Study Overview
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Brief Summary
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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.

Detailed Description
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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:

Official Title
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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

Conditions
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CMV Viremia, Immunosuppression-related Infectious Disease

Intervention / Treatment
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* Drug: Activated T-Lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 Patient with organic disease caused by CMV (confirmed by histology) resistant to antiviral first line treatment 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. 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 Documented genetic mutations associated with ganciclovir or foscarnet resistance ≥ 1 year of age Estimated life expectancy > 30 days Signature of the informed consent form Exclusion Criteria: Acute graft-versus-host disease (GVHD) ≥ grade II or chronic ≥ moderate Corticosteroid ≥ 0.5mg/kg regardless the indication Disease relapse at the time of infection or at any time after the Allogeneic transplant. Severe renal disease (creatinine > 3gr/dL) Severe hepatic disease (bilirubin >3mg/dL or aspartate aminotransferase (AST) >500 U/L) except if it is secondary to the viral infection. 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. 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 Known hypersensitivity to murine proteins or iron dextran. Positive serology to human immunodeficiency virus (HIV), hepatitis B virus (HBV) (HBsAg, HBcAc), hepatitis C virus (HCV) and/or syphilis Pregnant, lactating or women without adequate contraception Participation in a clinical trial with investigational medicinal products the last 30 days

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMV, Bone marrow transplant, Activated T-Lymphocytes, Cell therapy, Virus infection, immunosuppression