Using specialized T-cells to treat adenovirus infections in patients with immune deficiencies

A Pilot Study in the Treatment of Refractory Adenovirus (ADV) Infection With Related Donor ADV Cytotoxic T-Lymphocytes (ADV-CTLs)in Children, Adolescents and Young Adult Recipients

This study is testing whether special T-cells can help children, teens, and young adults with weak immune systems who have ongoing adenovirus infections after organ transplants.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 1 Month to 79 Years
• Sex: All
• Sponsor: New York Medical College (Academic / other)
• Drugs / interventions: prednisone
• Locations: 10 sites (Los Angeles, California and 9 other locations)
• Trial ID: NCT03266627 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to administer adenovirus-specific cytotoxic T-lymphocytes to children, adolescents, and young adults suffering from refractory adenovirus infections following allogeneic hematopoietic stem cell transplantation or solid organ transplantation. The T-cells are manufactured using the Miltenyi CliniMACS Prodigy Cytokine Capture System and are intended for patients who have persistent adenovirus infections despite antiviral therapy. The study focuses on patients with primary immune deficiencies or those who have undergone solid organ transplants and are experiencing severe symptoms related to adenovirus.

Who should consider this trial

Good fit: Ideal candidates include children, adolescents, and young adults with persistent adenovirus infections post-transplant and primary immune deficiencies.

Not a fit: Patients who do not have adenovirus infections or those who are not post-transplant may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with refractory adenovirus infections, potentially saving lives and enhancing recovery.

How similar studies have performed: Other studies utilizing T-cell therapies for viral infections have shown promise, indicating potential success for this approach.

Eligibility criteria

1. Patients with Adenovirus infections post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with:

   * Increasing or persistent quantitative ADV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or
   * clinical symptoms attributed to adenovirus, including pneumonitis, hemorrhagic cystitis, colitis, hepatitis AND/OR
   * Medical intolerance to anti-viral therapies including:

     * grade 2 renal insufficiency secondary to cidofovir 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 79 years

   Females of childbearing potential with a negative urine pregnancy test
2. Donor Eligibility Related donor available with a T-cell response to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

   a. Third Party Related 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 at least to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

   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.
3. 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 CTL infusion Patient receiving steroids (\>0.5 mg/kg prednisone equivalent) at the time of CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion 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 adenovirus infection(s) 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

\-

Where this trial is running

Los Angeles, California and 9 other locations

• Children's Hospital Los Angeles — Los Angeles, California, United States (Recruiting)
• University of California San Francisco — San Francisco, California, United States (Recruiting)
• Children's Hospital of Colorado — Aurora, Colorado, United States (Recruiting)
• University of Colorado Denver — Aurora, Colorado, United States (Recruiting)
• Indiana University — Indianapolis, Indiana, United States (Recruiting)
• Johns Hopkins — Baltimore, Maryland, United States (Not_yet_recruiting)
• Washington University — St Louis, Missouri, United States (Recruiting)
• Nationwide Children's Hosptial — Columbus, Ohio, United States (Recruiting)
• Children's Hospital of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• Medical College of Wisconsin/Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Mitchell Cairo, MD — New York Medical College
• Study coordinator: Mitchell Cairo, MD

Conditions Adenovirus; Primary Immune Deficiency Disorder; adenovirus; primary immune deficiency disorder; cytotoxic t-lymphocytes