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

Viral Infection Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04197596
• Other study ID #: NYMC 590
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: New York Medical College
• Contact: Mitchell S Cairo, MD
• Phone: 9145942150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Immunologic Deficiency Syndromes
• Infections
• Primary Immune Deficiency Disorder
• Primary Immunodeficiency Diseases
• Viral Infection
• Virus Diseases

Intervention

Biological:
• BK CTL
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).

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Johns Hopkins	Baltimore	Maryland
United States	Nationwide Children's Hosptial	Columbus	Ohio
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	New York Medical College	Valhalla	New York

Sponsors (6)

Lead Sponsor	Collaborator
New York Medical College	Children's Hospital of Philadelphia, Johns Hopkins University, Medical College of Wisconsin, Nationwide Children's Hospital, University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Patients will be monitored for adverse events following each CTL infusion	12 weeks