Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)

A Pilot Study in the Treatment of Refractory Cytomegalovirus (CMV) Infections With Related Donor CMV Specific Cytotoxic T-cells (CTLs) in Children, Adolescents and Young Adult Recipients

CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults (CAYA) with refractory cytomegalovirus (CMV) 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: Primary Immune Deficiency Disorder; Cytomegalovirus Infections
• Intervention / Treatment: Drug: viral specific cytotoxic t-lymphocytes

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

Contacts and Locations

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

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital 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
      • Not yet 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 month to 30 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. Patients with refractory CMV infection post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with either

• Increasing or persistent quantitative qRT-PCR DNA copies despite two weeks of appropriate anti-viral therapy AND/OR
• Medical intolerance to anti-viral therapies including:

• ANC < 500/mm2 secondary to ganciclovir

  • 2 renal toxicity with foscarnet And/or
• known resistance to ganciclovir and/or foscarnet

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

Donor Eligibility Related donor available with a T-cell response to the CMV MACS® GMP PepTivator antigen(s).

a. Third Party 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 CMV and/or a T-cell response to the CMV MACS® GMP PepTivator .

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 CMV CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CMV CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CMV CTL infusion Thymoglobulin (ATG), Alemtuzumab or T cell immunosuppressive monoclonal antibodies within 30 days Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% CMV retinitis Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory CMV 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 CMV retinitis, meningitis, encephalitis, and/or cerebritis

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 CMV; Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.	Drug: viral specific cytotoxic t-lymphocytes; CMV specific CTLs will be collected from HLA matched or mismatched donors and manufactured in a GMP facility and administered to patients with refractory CMV infection.; Other Names: CMV 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 following the administration of CMV CTLs	Patients will be followed for 12 weeks after each infusion
Incidence of Response to Treatment	Patients will be followed for improvement in viral infection by monitoring CMV PCR weekly for response to treatment with CTLs	Patients will be followed 12 weeks after each infusion

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• 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

• Keywords: Cytomegalovirus; CMV; cytotoxic t-lymphocytes
• Additional Relevant MeSH Terms: Virus Diseases; Immune System Diseases; Genetic Diseases, Inborn; DNA Virus Infections; Herpesviridae Infections; Infections; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Cytomegalovirus Infections
• Other Study ID Numbers: NYMC 580; 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