Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients (BK-CTLs)

A Pilot Study in the Treatment of BK Virus Infection With Cytotoxic T Cells in Immunocompromised Transplant Patients

This is a pilot study using cytotoxic T lymphocytes (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Gamma-capture system will be effective in decreasing specific viral load in patients with BK virus viremia and BK virus-associated symptoms post-allogeneic hematopoietic stem cell transplantation (HSCT), renal transplantation, and chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: BK Polyomavirus
• Intervention / Treatment: Biological: BK-virus specific CTLs

Detailed Description

This open-label, single-arm clinical trial will assess the safety and efficacy of BK virus-specific CTLs isolated from whole blood or leukapheresis products. The BK virus -specific CTLs will be generated automatically by the CliniMACS® Prodigy using the CliniMACS Cytokine Capture System (IFNgamma) after incubation with MACS GMP PepTivator® Peptide Pools of BKV VP1 and BKV LT.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Patricia Hankins, BSN, RN, CCRC; Phone Number: 215-590-5168; Email: hankinsp@chop.edu
• Study Contact Backup: Name: Meghan Rys, MS, CCRP; Phone Number: 215-590-6625; Email: rysm@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Nancy J Bunin, MD
      • Contact: Patricia Hankins, BSN, RN, CCRC; Phone Number: 215-590-5168; Email: hankinsp@chop.edu
      • Contact: Meghan Rys, MS, CCRP; Phone Number: 215-590-6625; Email: rysm@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patient Eligibility

• Patients with symptoms of cystitis and elevated BK virus DNA by screening PCR as above (section 4) post allogeneic HSCT, post chemotherapy

  1. Symptoms of cystitis may include: hematuria (microscopic or gross), pain with urination, frequency, bladder spasms.
  2. Patient may be otherwise treated for cystitis as per local institutional standards. Such treatments may include hydration, antiviral medications, or surgical intervention as deemed appropriate by treating physician.
• 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 25 years
• Females of childbearing potential with a negative urine pregnancy test.

Donor Eligibility

• Related donor available with a T-cell response to the BK-virus MACS® PepTivator® antigen(s).

  1. Original allogeneic donor if available, IgG positive for BKV or confirmatory testing to respond to BKV MACS Peptivator®.

  2. Third Party 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 to the BK MACS® 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.

Exclusion Criteria:

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 BK Virus CTL infusion
• Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of BK Virus CTL infusion or within 3 days of planned infusion.
• Thymoglobulin (ATG), campath 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%
• Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory BK virus 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: Supportive Care
• 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 cystitis and/or nephropathy; All patients with symptoms that are consistent with BK cystitis and/or nephropathy (frequency, dysuria, hematuria, elevated creatinine) will have serum quantitative DNA PCR for BK virus level measured in log copies per mL (results also expressed in copies per milliliter), performed in the Children's Hospital of Philadelphia Infectious Disease Diagnostics Laboratory

Biological: BK-virus specific CTLs; HLA Matched Related Donors: BK-virus 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). HLA Mismatched Related Donors: BK-virus 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
Number of participants with Grade III-IV acute GVHD	Number of participants with Grade III-IV acute GVHD as assessed by CTCAE v4.0	Up to 8 weeks after last BK-CTL infusion
Number of patients with undetectable BK viral load	Number of patients with undetectable BK viral load as measured by qPCR	12 weeks after first BK-CTL infusion

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Nancy J Bunin, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: 19-016545

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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