Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

NCT04293042 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 19-016545
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

BK Polyomavirus

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

BK cystitis and/or nephropathy

EXPERIMENTAL

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

Interventions

BK-virus specific CTLs BIOLOGICAL

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).

BK cystitis and/or nephropathy

Eligibility Criteria

• Age: 5 Weeks - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient Eligibility
• Patients with symptoms of cystitis and elevated BK virus DNA by screening PCR as above (section 4) post allogeneic HSCT, post chemotherapy
• Symptoms of cystitis may include: hematuria (microscopic or gross), pain with urination, frequency, bladder spasms.
• 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).
• Original allogeneic donor if available, IgG positive for BKV or confirmatory testing to respond to BKV MACS Peptivator®.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Study Officials

• Caitlin Elgarten, MD, MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Atkinson

CONTACT

215-590-2820; cttsbmtintake@chop.edu

Patricia Hankins, BSN, RN, CCRC

CONTACT

215-590-5168; hankinsp@chop.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Assistant Professor, Perelman School of Medicine at the University of Pennsylvania

Model Details: This open-label, single-arm clinical trial

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: March 3, 2020
• Study Start: October 7, 2019
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)