EBV-specific Cytotoxic T-lymphocytes (CTLs) for Refractory EBV Infection

Launched by NEW YORK MEDICAL COLLEGE · Aug 28, 2017

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for children, adolescents, and young adults with serious infections caused by the Epstein-Barr Virus (EBV) after they have undergone a stem cell transplant or organ transplant. The treatment involves using special immune cells called cytotoxic T-lymphocytes, which are made from related donors and are specifically designed to target and fight the EBV infection. The goal is to help patients who have not responded well to standard antiviral therapies.

To be eligible for this trial, participants must have ongoing EBV infections that have not improved despite receiving appropriate antiviral treatment. They also need to show specific symptoms related to the infection, such as swelling in the lymph nodes or liver. Participants must be between 0.1 and 79.99 years old, and a related donor with a suitable immune response to the virus must be available. Before joining the study, patients or their legal representatives must provide written consent. Throughout the study, participants can expect close monitoring and care from the medical team as they receive this new treatment.

Gender

ALL

Eligibility 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