RecruitingEarly Phase 1NCT04293042

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

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


Sponsor

Children's Hospital of Philadelphia

Enrollment

20 participants

Start Date

Oct 7, 2019

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 5 WeeksMax Age: 25 Years

Inclusion Criteria16

  • 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
  • Obtained informed consents by donor or donor legally authorized representative prior to donor collection.

Exclusion Criteria12

  • 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

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Interventions

BIOLOGICALBK-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).


Locations(1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

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NCT04293042


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