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

Primary Purpose

Epstein-Barr Virus Infections, Primary Immune Deficiency Disorder

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cytotoxic t-lymphocytes
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epstein-Barr Virus Infections

Eligibility Criteria

1 Month - 79 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hosptial Los AngelesRecruiting
  • University of California San FranciscoRecruiting
  • Johns HopkinsRecruiting
  • Washington UniversityRecruiting
  • New York Medical CollegeRecruiting
  • Nationwide Children's HosptialRecruiting
  • Children's Hospital of PennsylvaniaRecruiting
  • Medical College of Wisconsin/Children's Hospital of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Refractory EBV

Arm Description

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)

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Patients will be monitored for adverse events related to the infusion of EBV CTLs
Incidence of Response to Treatment [Efficacy]
Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs

Secondary Outcome Measures

Full Information

First Posted
August 25, 2017
Last Updated
October 24, 2023
Sponsor
New York Medical College
Collaborators
Children's Hospital of Philadelphia, Medical College of Wisconsin, Nationwide Children's Hospital, Indiana University, Washington University School of Medicine, University of California, Los Angeles, University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT03266653
Brief Title
EBV-specific Cytotoxic T-lymphocytes (CTLs) for Refractory EBV Infection
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 7, 2020 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
Children's Hospital of Philadelphia, Medical College of Wisconsin, Nationwide Children's Hospital, Indiana University, Washington University School of Medicine, University of California, Los Angeles, University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Infections, Primary Immune Deficiency Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
All patients given identical treatment with CTLs for refractory EBV.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Refractory EBV
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
cytotoxic t-lymphocytes
Other Intervention Name(s)
CTLs
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Patients will be monitored for adverse events related to the infusion of EBV CTLs
Time Frame
Patients will be followed for 12 weeks after each infusion
Title
Incidence of Response to Treatment [Efficacy]
Description
Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs
Time Frame
Patients will be followed for 12 weeks after each infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility 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 79.99 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mitchell Cairo, MD
Phone
914-594-2150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Harrison
Phone
6172857844
Email
lauren_harrison@nymc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell Cairo, MD
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hosptial Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neena Kapoor, MD
Email
nkapoor@chla.usc.edu
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Chu, MD
Email
Julia.Chu2@ucsf.edu
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Cooke, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shalini Shenoy, MD
Email
shalinishenoy@wustl.edu
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mitchell S Cairo, MD
Phone
914-594-2150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name & Degree
Mitchell S. Cairo, MD
Facility Name
Nationwide Children's Hosptial
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dean Lee, MD, PhD
Phone
614-722-3550
Email
Dean.Lee@nationwidechildrens.org
Facility Name
Children's Hospital of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Bunin, MD
Phone
215-590-2255
Email
buninn@email.chop.edu
Facility Name
Medical College of Wisconsin/Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie A Talano, MD
Phone
414-955-4185
Email
jtalano@mcw.edu
First Name & Middle Initial & Last Name & Degree
Kathy Jodarski
Phone
414-266-2681
Email
kjodarski@chw.org

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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