Clinical trial NCT04197596: Treatment of Refractory BK Infections With Related Donor BK Specific Cytotoxic T-cells (CTLs)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Viral Infection
Primary Immune Deficiency Disorder
Lead sponsor: New York Medical College
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
name: Medical College of Wisconsin
name: Nationwide Children's Hospital
name: Johns Hopkins University
name: University of California, San Francisco
First posted: 2019-12-13
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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:

1. Patient with acute GVHD \> grade 2 or extensive chronic GVHD at the time of BK CTL infusion
2. Patient receiving steroids (\>0.5 mg/kg prednisone equivalent) at the time of BK CTL infusion
3. Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to BK CTL infusion
4. Thymoglobulin (ATG) or Alemtuzumab within 30 days
5. Patient with poor performance status determined by Karnofsky (patients \>16 years) or Lansky (patients ≤16 years) score ≤30%
6. Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory BK infection.
7. Any medical condition which could compromise participation in the study according to the investigator's assessment
8. Known HIV infection
9. 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.
10. Known hypersensitivity to iron dextran
11. Patients unwilling or unable to comply with the protocol or unable to give informed consent.
12. Known human anti-mouse antibodies

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hosptial
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Pennsylvania
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: New York Medical College
name: Mitchell S Cairo, MD
role: PRINCIPAL_INVESTIGATOR
References: