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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Viral Infection, Primary Immune Deficiency Disorder

Intervention / Treatment
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* Biological: BK CTL


Participation Criteria
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Eligibility Criteria
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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: Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of BK CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of BK CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to BK CTL infusion Thymoglobulin (ATG) or Alemtuzumab 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 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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BK CTL<br>Eligible patients with refractory BK infection will receive up to 5 infusions of BK CTLs that are donor derived. | Biological: BK CTL<br>* 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).<br>|

What is the study measuring?
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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 |