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出境医 / 临床实验 / Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients

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

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.


Condition or disease Intervention/treatment Phase
CMV Viremia Immunosuppression-related Infectious Disease Drug: Activated T-Lymphocytes Phase 1 Phase 2

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : April 2022
Arms and Interventions
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
Outcome Measures
Primary Outcome Measures :
  1. Safety assessment: Adverse events [ Time Frame: 60 days ]
    Adverse events


Secondary Outcome Measures :
  1. Polymerase chain reaction (PCR) [ Time Frame: +7, +14, +21, +28, +45, +60 days ]
    Quantitative viral load

  2. IFN-γ+ spot forming cells [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by Elispot

  3. Lymphocyte subpopulations [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by flow cytometry

  4. T-cell persistence by chimerism [ Time Frame: +14, +28 days ]
    Detection of donor cellularity (administered product) in the receptor serum

  5. Time elapsed in identifying the donor [ Time Frame: Day 0 ]
    Time elapsed between the patient's inclusion in the trial and confirmation of the donor


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Contacts
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Contact: Ruth Coll, MD +34935573500 ext 6707 rucoll@bst.cat

Locations
Layout table for location information
Spain
ICO Badalona Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Christelle Ferrá, MD, PhD    +34 934651200    cferra@iconcologia.net   
Principal Investigator: Christelle Ferrá, MD, PhD         
Hospital Sant Joan de Déu Recruiting
Esplugues De Llobregat, Barcelona, Spain, 08950
Contact: Júlia Marsal, MD, PhD    +34 932532100    jmarsal@sjdhospitalbarcelona.org   
Principal Investigator: Júlia Marsal, MD, PhD         
Sub-Investigator: Izaskun Elorza Elorza, MD, PhD         
ICO l'Hospitalet Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Contact: Rocio Parody, MD, PhD    +34 932607733    rparody@iconcologia.net   
Principal Investigator: Rocio Parody, MD, PhD         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Rodrigo Martino, MD, PhD    +34 935565649    RMartino@santpau.cat   
Principal Investigator: Rodrigo Martino, MD, PhD         
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Pere Barba, MD, PhD    +34 934893000    pbarba@vhio.net   
Principal Investigator: Pere Barba, MD, PhD         
Sub-Investigator: Laura Alonso, MD, PhD         
Sub-Investigator: Guillermo Ortí, MD, PhD         
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Montserrat Rovira, MD, PhD    +34 932275400    mrovira@clinic.cat   
Principal Investigator: Montserrat Rovira, MD, PhD         
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46026
Contact: Juan Montoro, MD    +34 961244000    juanmontorogomez@gmail.com   
Principal Investigator: Juan Montoro, MD         
Sub-Investigator: Manuel Guerreiro, MD, PhD         
Sponsors and Collaborators
Banc de Sang i Teixits
Vall d'Hebron Institute of Oncology
Hospital Universitario La Fe
Investigators
Layout table for investigator information
Principal Investigator: Pere Barba, MD, PhD VHIO (Vall d'Hebron Institute of Oncology)
Tracking Information
First Submitted Date  ICMJE July 9, 2019
First Posted Date  ICMJE July 12, 2019
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE July 4, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019) 		Safety assessment: Adverse events [ Time Frame: 60 days ]
Adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2019)
  • Polymerase chain reaction (PCR) [ Time Frame: +7, +14, +21, +28, +45, +60 days ]
    Quantitative viral load
  • IFN-γ+ spot forming cells [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by Elispot
  • Lymphocyte subpopulations [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by flow cytometry
  • T-cell persistence by chimerism [ Time Frame: +14, +28 days ]
    Detection of donor cellularity (administered product) in the receptor serum
  • Time elapsed in identifying the donor [ Time Frame: Day 0 ]
    Time elapsed between the patient's inclusion in the trial and confirmation of the donor
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • Polymerase chain reaction (PCR) [ Time Frame: +7, +14, +21, +28, +45, +60 days ]
    Quantitative viral load
  • Immune reconstitution by Elispot [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by Elispot
  • Immune reconstitution by flow cytometry [ Time Frame: +7, +14, +28, +60 days ]
    Immune reconstitution by flow cytometry
  • T-cell persistence by chimerism [ Time Frame: +14, +28 days ]
    Detection of donor cellularity (administered product) in the receptor serum
  • Time elapsed in identifying the donor [ Time Frame: Day 0 ]
    Time elapsed between the patient's inclusion in the trial and confirmation of the donor
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Virus-specific Activated T Lymphocytes From a Donor in Hematopoietic Progenitor Transplanted Patients
Official Title  ICMJE 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
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:
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CMV Viremia
  • Immunosuppression-related Infectious Disease
Intervention  ICMJE Drug: Activated T-Lymphocytes
Activated T-Lymphocytes will be infused intravenously in a single-dose
Study Arms  ICMJE Experimental: Activated T-Lymphocytes
Allogeneic T-Lymphocytes obtained from apheresis activated against CMV.
Intervention: Drug: Activated T-Lymphocytes
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ruth Coll, MD +34935573500 ext 6707 rucoll@bst.cat
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04018261
Other Study ID Numbers  ICMJE BST-LT-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Banc de Sang i Teixits
Study Sponsor  ICMJE Banc de Sang i Teixits
Collaborators  ICMJE
  • Vall d'Hebron Institute of Oncology
  • Hospital Universitario La Fe
Investigators  ICMJE
Principal Investigator: Pere Barba, MD, PhD VHIO (Vall d'Hebron Institute of Oncology)
PRS Account Banc de Sang i Teixits
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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