Using EBV-specific T-cells to treat difficult Epstein-Barr virus infections
A Pilot Study in the Treatment of Refractory Epstein-Barr Virus (EBV) Infection With Related Donor EBV Cytotoxic T-Lymphocytes in Children, Adolescents and Young Adult Recipients
This study is testing a new treatment using specially made immune cells to help children and young adults who have tough Epstein-Barr virus infections after receiving 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 | rituximab, prednisone |
| Locations | 8 sites (Los Angeles, California and 7 other locations) |
| Trial ID | NCT03266653 on ClinicalTrials.gov |
What this trial studies
This clinical trial focuses on administering Epstein-Barr virus (EBV) specific cytotoxic T-lymphocytes (CTLs) to children, adolescents, and young adults who have refractory EBV infections following allogeneic hematopoietic stem cell transplantation or solid organ transplantation. The CTLs are manufactured using the Miltenyi CliniMACS Prodigy Cytokine Capture System and aim to target persistent EBV infections that do not respond to standard antiviral therapies. Participants will be monitored for clinical improvements and changes in EBV viral load following treatment.
Who should consider this trial
Good fit: Ideal candidates include children, adolescents, and young adults with persistent EBV infections post-transplantation who have not responded to antiviral therapies.
Not a fit: Patients with EBV infections that are not refractory or those who do not meet the eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from refractory EBV infections, potentially improving their health outcomes.
How similar studies have performed: Other studies utilizing EBV-specific T-cells have shown promise, suggesting that this approach may be effective in treating similar conditions.
Eligibility criteria
Show full inclusion / exclusion criteria
1\. Patients with Epstein-Barr virus infections post allogeneic HSCT, primary immunodeficiencies or post solid organ transplant with: * Increasing or persistent quantitative EBV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or * progressive clinical symptoms attributable to EBV, including biopsy proven colitis, lymphadenopathy, hepatomegaly, splenomegaly AND/OR * Medical intolerance to anti-viral therapies including: * intolerance to rituximab 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 79.99 years Females of childbearing potential with a negative urine pregnancy test 2 Donor Eligibility 5.2.1 Related donor available with a T-cell response to the EBV MACS® GMP PepTivator antigen(s) causing the therapy-refractory EBV infection. a. Third Party Related Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party related allogeneic donor (family donor \> 1 HLA A, B, DR match to recipient) with IgG positive to EBV and/or a T-cell response at least to the viral MACS® GMP PepTivator EBV Select (containing among other antigens, NA-1, LMP2A and BZLF-1). 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 EBV 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
Where this trial is running
Los Angeles, California and 7 other locations
- Children's Hosptial Los Angeles — Los Angeles, California, United States (Recruiting)
- University of California San Francisco — San Francisco, California, United States (Recruiting)
- Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
- Washington University — St Louis, Missouri, United States (Recruiting)
- New York Medical College — Valhalla, New York, 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
- Email: mitchell_cairo@nymc.edu
- Phone: 914-594-2150
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.