Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients
Primary Purpose
CMV Viremia, Immunosuppression-related Infectious Disease
Status
Active
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Activated T-Lymphocytes
Sponsored by
About this trial
This is an interventional treatment trial for CMV Viremia focused on measuring CMV, Bone marrow transplant, Activated T-Lymphocytes, Cell therapy, Virus infection, immunosuppression
Eligibility Criteria
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
Sites / Locations
- ICO Badalona
- Hospital Sant Joan de Déu
- ICO l'Hospitalet
- Hospital de la Santa Creu i Sant Pau
- Hospital Vall d'Hebron
- Hospital Clinic i Provincial de Barcelona
- Hospital Universitario La Fe
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Activated T-Lymphocytes
Arm Description
Allogeneic T-Lymphocytes obtained from apheresis activated against CMV.
Outcomes
Primary Outcome Measures
Safety assessment: Adverse events
Adverse events
Secondary Outcome Measures
Polymerase chain reaction (PCR)
Quantitative viral load
IFN-γ+ spot forming cells
Immune reconstitution by Elispot
Lymphocyte subpopulations
Immune reconstitution by flow cytometry
T-cell persistence by chimerism
Detection of donor cellularity (administered product) in the receptor serum
Time elapsed in identifying the donor
Time elapsed between the patient's inclusion in the trial and confirmation of the donor
Full Information
NCT ID
NCT04018261
First Posted
July 9, 2019
Last Updated
July 14, 2023
Sponsor
Banc de Sang i Teixits
Collaborators
Vall d'Hebron Institute of Oncology, Hospital Universitario La Fe
1. Study Identification
Unique Protocol Identification Number
NCT04018261
Brief Title
Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 4, 2019 (Actual)
Primary Completion Date
October 18, 2021 (Actual)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Banc de Sang i Teixits
Collaborators
Vall d'Hebron Institute of Oncology, Hospital Universitario La Fe
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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:
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CMV Viremia, Immunosuppression-related Infectious Disease
Keywords
CMV, Bone marrow transplant, Activated T-Lymphocytes, Cell therapy, Virus infection, immunosuppression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Activated T-Lymphocytes
Arm Type
Experimental
Arm Description
Allogeneic T-Lymphocytes obtained from apheresis activated against CMV.
Intervention Type
Drug
Intervention Name(s)
Activated T-Lymphocytes
Intervention Description
Activated T-Lymphocytes will be infused intravenously in a single-dose
Primary Outcome Measure Information:
Title
Safety assessment: Adverse events
Description
Adverse events
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Polymerase chain reaction (PCR)
Description
Quantitative viral load
Time Frame
+7, +14, +21, +28, +45, +60 days
Title
IFN-γ+ spot forming cells
Description
Immune reconstitution by Elispot
Time Frame
+7, +14, +28, +60 days
Title
Lymphocyte subpopulations
Description
Immune reconstitution by flow cytometry
Time Frame
+7, +14, +28, +60 days
Title
T-cell persistence by chimerism
Description
Detection of donor cellularity (administered product) in the receptor serum
Time Frame
+14, +28 days
Title
Time elapsed in identifying the donor
Description
Time elapsed between the patient's inclusion in the trial and confirmation of the donor
Time Frame
Day 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pere Barba, MD, PhD
Organizational Affiliation
VHIO (Vall d'Hebron Institute of Oncology)
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICO Badalona
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Sant Joan de Déu
City
Esplugues De Llobregat
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
ICO l'Hospitalet
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.bancsang.net
Description
Blood and Tissue Bank of Catalonia
URL
http://www.vhio.net
Description
Vall d'Hebron Institute of Oncology
Learn more about this trial
Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients
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