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

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.

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

• 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 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