Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

A Pilot Study in the Treatment of Refractory Adenovirus (ADV) Infection With Related Donor ADV Cytotoxic T-Lymphocytes (ADV-CTLs)in Children, Adolescents and Young Adult Recipients

Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in children, adolescents and young adults with refractory ADV 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; Adenovirus
• Intervention / Treatment: Drug: cytotoxic t-lymphocytes

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

Contacts and Locations

• Study Contact: Name: Lauren Harrison, RN; Phone Number: 617-285-7844; 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 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
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital of Colorado
      • Contact: Michael Verneris, MD; Phone Number: 720-777-1234; Email: Michael.Verneris@childrenscolorado.org
      • Contact: Amanda Kinderman, MPH; Phone Number: 303-724-3652; Email: amanda.kinderman@ucdenver.edu
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver
      • Contact: Michael Verneris, MD; Email: MICHAEL.VERNERIS@CUANSCHUTZ.EDU
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Emily Hopewell, MD; Email: emlhope@iu.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
  • 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: Meredith Beversdorf, RN; Phone Number: (414) 266-5891; Email: mbeversdorf@mcw.edu

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 Adenovirus infections post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with:

   • Increasing or persistent quantitative ADV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or
   • clinical symptoms attributed to adenovirus, including pneumonitis, hemorrhagic cystitis, colitis, hepatitis AND/OR

   • Medical intolerance to anti-viral therapies including:

     • grade 2 renal insufficiency secondary to cidofovir 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 years

   Females of childbearing potential with a negative urine pregnancy test

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

   a. Third Party Related Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with a T-cell response at least to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

   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 adenovirus infection(s) 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: patients with adenoviral infection; patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.	Drug: cytotoxic t-lymphocytes; adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.; Other Names: viral specific 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 followed for adverse events following each infusion of ADV CTLs	12 weeks after each infusion
Incidence of Response to Treatment (Efficacy)	Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs	12 weeks after last infusion

Collaborators and Investigators

• Sponsor: New York Medical College
• Collaborators: Johns Hopkins University; University of Colorado, Denver; 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): November 1, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 25, 2017
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (Actual): August 30, 2017

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: adenovirus; primary immune deficiency disorder; cytotoxic t-lymphocytes
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Infections; Virus Diseases; DNA Virus Infections; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Adenoviridae Infections
• Other Study ID Numbers: NYMC 579; 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