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

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

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

Study Overview

• Status: Recruiting
• Conditions: Epstein-Barr Virus Infections; Primary Immune Deficiency Disorder
• Intervention / Treatment: Drug: cytotoxic t-lymphocytes

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lauren Harrison; Phone Number: 6172857844; Email: lauren_harrison@nymc.edu
• Study Contact Backup: Name: Mitchell Cairo, MD; Phone Number: 914-594-2150; Email: mitchell_cairo@nymc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hosptial Los Angeles
      • Contact: Neena Kapoor, MD; Email: nkapoor@chla.usc.edu
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
      • Contact: Julia Chu, MD; Email: Julia.Chu2@ucsf.edu
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins
      • Contact: Kenneth Cooke, MD
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University
      • Contact: Shalini Shenoy, MD; Email: shalinishenoy@wustl.edu
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • New York Medical College
      • Contact: Mitchell S Cairo, MD; Phone Number: 914-594-2150; Email: mitchell_cairo@nymc.edu
      • Principal Investigator: Mitchell S. Cairo, MD
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hosptial
      • Contact: Dean Lee, MD, PhD; Phone Number: 614-722-3550; Email: Dean.Lee@nationwidechildrens.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Pennsylvania
      • Contact: Nancy Bunin, MD; Phone Number: 215-590-2255; Email: buninn@email.chop.edu
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin/Children's Hospital of Wisconsin
      • Contact: Julie A Talano, MD; Phone Number: 414-955-4185; Email: jtalano@mcw.edu
      • Contact: Kathy Jodarski; Phone Number: 414-266-2681; Email: kjodarski@chw.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 28 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: CTLs

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: New York Medical College
• Collaborators: Children's Hospital of Philadelphia; Washington University School of Medicine; University of California, Los Angeles; Medical College of Wisconsin; University of California, San Francisco; Nationwide Children's Hospital; Indiana University
• Investigators: Principal Investigator: Mitchell Cairo, MD, New York Medical College

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 25, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (Actual): August 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Immune System Diseases; Disease Attributes; Genetic Diseases, Inborn; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Epstein-Barr Virus Infections
• Other Study ID Numbers: NYMC 581; FD006363 (Other Grant/Funding Number: FDA OOPD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No