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EBV-specific Cytotoxic T-lymphocytes (CTLs) for Refractory EBV Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03266653
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : July 20, 2020
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Medical College of Wisconsin
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Brief Summary:

Related donor Epstein-Barr Virus (EBV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults with refractory EBV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant.

Funding Source: FDA OOPD


Condition or disease Intervention/treatment Phase
Epstein-Barr Virus Infections Primary Immune Deficiency Disorder Drug: cytotoxic t-lymphocytes Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All patients given identical treatment with CTLs for refractory EBV.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study in the Treatment of Refractory Epstein-Barr Virus (EBV) Infection With Related Donor EBV Cytotoxic T-Lymphocytes in Children, Adolescents and Young Adult Recipients
Actual Study Start Date : July 7, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Refractory EBV
Patients with refractory EBV will get one dose of EBV specific CTLs. If they don't show a response based on EBV PCRs, patients may get up to another 4 doses of EBV-CTLs (5 doses maximum)
Drug: cytotoxic t-lymphocytes
EBV specific CTLs will be generated from HLA related matched and mismatched donors in a GMP facility and administered to the patient with refractory CTLs.
Other Name: CTLs




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Patients will be followed for 12 weeks after each infusion ]
    Patients will be monitored for adverse events related to the infusion of EBV CTLs

  2. Incidence of Response to Treatment [Efficacy] [ Time Frame: Patients will be followed for 12 weeks after each infusion ]
    Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

1. Patients with Epstein-Barr virus infections post allogeneic HSCT, primary immunodeficiencies or post solid organ transplant with:

  • Increasing or persistent quantitative EBV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or
  • progressive clinical symptoms attributable to EBV, including biopsy proven colitis, lymphadenopathy, hepatomegaly, splenomegaly AND/OR
  • Medical intolerance to anti-viral therapies including:
  • intolerance to rituximab Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures.

Performance Status > 30% (Lansky < 16 yrs and Karnofsky > 16 yrs) Age: 0.1 to 30.99 years Females of childbearing potential with a negative urine pregnancy test

2 Donor Eligibility 5.2.1 Related donor available with a T-cell response to the EBV MACS® GMP PepTivator antigen(s) causing the therapy-refractory EBV infection.

a. Third Party Related Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party related allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with IgG positive to EBV and/or a T-cell response at least to the viral MACS® GMP PepTivator EBV Select (containing among other antigens, NA-1, LMP2A and BZLF-1).

AND Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1).

AND Obtained informed consents by donor or donor legally authorized representative prior to donor collection.

3 Patient exclusion criteria:

A patient meeting any of the following criteria is not eligible for the present study:

Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory EBV infection Any medical condition which could compromise participation in the study according to the investigator's assessment Known HIV infection Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.

Known hypersensitivity to iron dextran Patients unwilling or unable to comply with the protocol or unable to give informed consent.

Known human anti-mouse antibodies


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): NCT03266653


Contacts
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Contact: Mitchell Cairo, MD 914-594-2150 mitchell_cairo@nymc.edu
Contact: Lauren Harrison 6172857844 lauren_harrison@nymc.edu

Locations
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United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-2150    mitchell_cairo@nymc.edu   
Principal Investigator: Mitchell S. Cairo, MD         
United States, Ohio
Nationwide Children's Hosptial Recruiting
Columbus, Ohio, United States, 43205
Contact: Dean Lee, MD, PhD    614-722-3550    Dean.Lee@nationwidechildrens.org   
United States, Pennsylvania
Children's Hospital of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nancy Bunin, MD    215-590-2255    buninn@email.chop.edu   
United States, Wisconsin
Medical College of Wisconsin/Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie A Talano, MD    414-955-4185    jtalano@mcw.edu   
Contact: Kathy Jodarski    414-266-2681    kjodarski@chw.org   
Sponsors and Collaborators
New York Medical College
Children's Hospital of Philadelphia
Medical College of Wisconsin
Investigators
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Principal Investigator: Mitchell Cairo, MD New York Medical College
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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT03266653    
Other Study ID Numbers: NYMC 581
FD006363 ( Other Grant/Funding Number: FDA OOPD )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Epstein-Barr Virus Infections
Immunologic Deficiency Syndromes
Virus Diseases
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections