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

Sponsor
New York Medical College (Other)
Overall Status
Recruiting
CT.gov ID
NCT04197596
Collaborator
Children's Hospital of Philadelphia (Other), Medical College of Wisconsin (Other), Nationwide Children's Hospital (Other), Johns Hopkins University (Other), University of California, San Francisco (Other)
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Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Biological: BK CTL
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 1, 2020
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: BK CTL

Eligible patients with refractory BK infection will receive up to 5 infusions of BK CTLs that are donor derived.

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).

Outcome Measures

Primary Outcome Measures

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [12 weeks]

    Patients will be monitored for adverse events following each CTL infusion

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Month to 30 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 30.99 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California San Francisco San Francisco California United States 94158
2 Johns Hopkins Baltimore Maryland United States 21287
3 New York Medical College Valhalla New York United States 10595
4 Nationwide Children's Hosptial Columbus Ohio United States 43205
5 Children's Hospital of Pennsylvania Philadelphia Pennsylvania United States 19104
6 Medical College of Wisconsin Milwaukee Wisconsin United States 53226

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: Mitchell S Cairo, MD, New York Medical College

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
New York Medical College
ClinicalTrials.gov Identifier:
NCT04197596
Other Study ID Numbers:
  • NYMC 590
First Posted:
Dec 13, 2019
Last Update Posted:
Feb 23, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 23, 2021