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Trial record 9 of 80 for:    Recruiting, Not yet recruiting, Available Studies | "Epstein-Barr Virus Infections"

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES)

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ClinicalTrials.gov Identifier: NCT03475212
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Michael Pulsipher, MD, Children's Hospital Los Angeles

Brief Summary:
The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infections Adenovirus Infection EBV Infection Biological: Virus Specific T-cell (VST) infusion Phase 1 Phase 2

Detailed Description:

The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus.

Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in preventing and treating infections associated with CMV, EBV and adenovirus post-transplant. However, the time required to prepare patient-specific products and lack of virus-specific memory T cells in cord blood and seronegative donors, limits their value. An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior phase II study at Baylor College of Medicine using trivirus-specific VSTs generated using monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral vector expressing CMV-pp65 to activate and expand specific T cells showed the feasibility, safety and activity of this approach for the treatment of refractory CMV, EBV and Adenovirus infections. More recent protocols utilizing synthetic viral peptide pools allow ex vivo expansion of T-cells targeting multiple viral antigens in 10-12 days without use of viral transduction.

The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.

This study will evaluate safety and efficacy of partially-matched VST therapy in A) patients who have persistent viral infections in the post-HSCT period, and B) patients with primary immunodeficiency conditions who have persistent viral infections and have not undergone HSCT.

The study agent will be assessed for safety and antiviral activity.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES) PBMTC SUP1701
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Virus specific T cell lines (VSTs) against three viruses
The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.
Biological: Virus Specific T-cell (VST) infusion
Patients will receive partially HLA-matched VSTs as a single infusion. Patients who have a partial response (>1 log decrease in viral load without clearance) or no response and do not have treatment-related dose-limiting toxicities are eligible to receive up to 3 additional doses from day 30 after the initial infusion and at 2 weekly intervals thereafter. The viral load of the virus (or viruses) that patients are initially treated for are monitored by viral PCR.




Primary Outcome Measures :
  1. Feasibility to identify suitable HLA matched VST products [ Time Frame: 30 days ]
    Feasibility will be defined as the ability of the investigators to identify suitable partially HLA- matched VST products from the VST bank at Children's National Medical Center for referred study subjects. The percentage of referred patients with potential partially-matched VST products identified will be recorded, as will timing between patient referral and treatment.

  2. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 30 days ]
    The safety endpoint, dose-limiting toxicity (DLT), will be defined as acute GvHD grades III-IV or grades 3-5 infusion-related adverse events or grades 4-5 non-hematological adverse events related to the T cell product within 30 days of each VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.

  3. Efficacy of VST at 30 days as measured by viral load [ Time Frame: 30 days ]
    Peripheral blood and, where relevant, stool and urine will be monitored for CMV, EBV, and/or adenovirus viral load. For patients with multiple viral infections, the response against the primary viral target will determine the classification. For the infection under treatment response in viral load will be assessed at 30 days after the first VST infusion



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients who have received any type of allogeneic transplant or who have a primary immunodeficiency disorder will be eligible if they have CMV, adenovirus, and/or EBV infection/disease with failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy.

  • Patients must meet one of the following criteria:

    • Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cell or single or double cord blood within the previous 18 months, OR
    • Have a diagnosed primary immunodeficiency disorder (as defined by clinical and laboratory evaluations) and not undergone HSCT.
  • Treatment of the following persistent or relapsed infections despite standard therapy:

    • CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy. For CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir for at least 14 days.
    • Adenovirus: Treatment of persistent or relapsed adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or brincidofovir.
    • EBV: Treatment of persistent or relapsed EBV infection despite standard therapy.

For EBV infection, standard therapy is defined as rituximab given at 375 mg/m2 in patients for 1-4 doses with a CD20+ tumor.

Additional Inclusion Criteria:

  • Patients with simultaneous infections with CMV, EBV and/or Adenovirus infections are eligible if one or more infection(s) is persistent or relapsed despite standard therapy as defined above. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
  • Clinical status at enrollment that allows tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent) prior to infusion of the VST doses.
  • Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
  • Written informed consent and/or signed assent line from patient, parent or guardian.

Exclusion Criteria

  • Patients receiving ATG, Campath, Basiliximab or other immunosuppressive monoclonal antibodies targeting T-cells within 28 days of screening for enrollment.
  • Patients who have received donor lymphocyte infusion (DLI) or other experimental cellular therapies within 28 days.
  • Current therapy with ruxolitinib or other JAK inhibitors within the previous 3 days.
  • Patients with other uncontrolled infections, defined as bacterial or fungal infections with clinical signs of worsening despite standard therapy. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
  • Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Patients with active and uncontrolled relapse of malignancy (if applicable).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03475212


Contacts
Contact: Elena Eckroth 323-361-3158 eeckroth@chla.usc.edu

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 91016
Contact: Elena Eckroth    323-361-3158    eeckroth@chla.usc.edu   
Principal Investigator: Michael Pulsipher, MD         
United States, Texas
Methodist Healthcare System of San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Candace Taylor    210-575-7379    candace.taylor@mhshealth.com   
Principal Investigator: Troy Quigg, DO         
Sponsors and Collaborators
Michael Pulsipher, MD
Investigators
Study Chair: Michael Pulsipher, MD Children's Hospital Los Angeles
Study Chair: Michael Keller, MD Children's Research Institute

Responsible Party: Michael Pulsipher, MD, Principal Investigator, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT03475212     History of Changes
Other Study ID Numbers: PBMTC SUP1701
First Posted: March 23, 2018    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Pulsipher, MD, Children's Hospital Los Angeles:
Hematopoietic Stem Cell Transplant
Primary Immune Deficiency Disease

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Infection
Communicable Diseases
Cytomegalovirus Infections
Adenoviridae Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Antiviral Agents
Anti-Infective Agents