Treatment of Refractory BK Infections With Related Donor BK Specific Cytotoxic T-cells (CTLs)

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

BK cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be safe and effective in decreasing specific viral load in children, adolescents and young adults (CAYA) with refractory BK infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) or with primary immunodeficiencies (PID).

Study Overview

• Status: Recruiting
• Conditions: Primary Immune Deficiency Disorder; Viral Infection
• Intervention / Treatment: Biological: BK CTL

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lauren Harrison; Phone Number: 16172857844; Email: lauren_harrison@nymc.edu
• Study Contact Backup: Name: Mitchell S Cairo, MD; Phone Number: 9145942150; Email: mitchell_cairo@nymc.edu

Study Locations

• United States
  • California
    • 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
  • 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
      • Contact: Lauren Harrison, RN; Phone Number: 6172857844; Email: lauren_harrison@nymc.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
      • Contact: Julie A Talano, MD; Phone Number: 414-955-4185; Email: jtalano@mcw.edu
      • Principal Investigator: Julie A Talano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 30 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

.1.1 Patients with refractory BK infection post allogeneic HSCT, post solid organ transplantation or with primary immunodeficiencies with either

• Increasing urine and/or plasma BK RT-PCR DNA (by 1 log) after 7 days or persistent quantitative qRT-PCR DNA copies after 14 days despite two weeks of appropriate anti-viral therapy AND/OR

• Medical intolerance to anti-viral therapies including:

  • 2 renal toxicity with cidofovir or other > grade 2 toxicities secondary to cidofovir And/or
• known resistance to cidofovir 1.2. Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures.

1.3 Performance Status > 30% (Lansky < 16 yrs and Karnofsky > 16 yrs) 1.4 Age: 0.1 to 79.99 years 1.5 Females of childbearing potential with a negative urine pregnancy test

Exclusion:

1. Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of BK CTL infusion
2. Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of BK CTL infusion
3. Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to BK CTL infusion
4. Thymoglobulin (ATG) or Alemtuzumab within 30 days
5. Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30%
6. Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory BK infection.
7. Any medical condition which could compromise participation in the study according to the investigator's assessment
8. Known HIV infection
9. 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.
10. Known hypersensitivity to iron dextran
11. Patients unwilling or unable to comply with the protocol or unable to give informed consent.
12. 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: BK CTL; Eligible patients with refractory BK infection will receive up to 5 infusions of BK CTLs that are donor derived.

Biological: BK CTL; Patient with refractory BK infection and a HLA Matched Related Donors: BK specific CTLs (2.5 x 104 CD3/kg) infused intravenously on day 0 and may be additionally reinfused at a minimum of every two weeks (depending on safety and efficacy) for a maximum of five total infusions (maximum 12.5 x 104 CD3/kg). Patients with refractory BK virus and a HLA Mismatched Related Donors: BK specific CTLs (0.5x104 CD3/kg) infused intravenously on day 0 and may additionally be reinfused at a minimum of every two weeks (depending on safety and efficacy) for a maximum of five total infusions (maximum 2.5 x 104 CD3/kg).

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 each CTL infusion	12 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 11, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 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; Immune System Diseases; Disease Attributes; Genetic Diseases, Inborn; Infections; Communicable Diseases; Virus Diseases; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
• Other Study ID Numbers: NYMC 590

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