Epstein-Barr Virus Infections, Primary Immune Deficiency Disorder
Conditions
Brief summary
Related donor Epstein-Barr Virus (EBV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults with refractory EBV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD
Interventions
EBV specific CTLs will be generated from HLA related matched and mismatched donors in a GMP facility and administered to the patient with refractory CTLs.
Sponsors
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Indiana University
Washington University School of Medicine
University of California, Los Angeles
University of California, San Francisco
New York Medical College
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients given identical treatment with CTLs for refractory EBV.
Eligibility
Sex/Gender
ALL
Age
1 Months to 79 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Patients will be followed for 12 weeks after each infusion | Patients will be monitored for adverse events related to the infusion of EBV CTLs |
| Incidence of Response to Treatment [Efficacy] | Patients will be followed for 12 weeks after each infusion | Patients will be followed for improvement in viral infection by monitoring EBV PCR weekly for response to treatment with CTLs |
Countries
United States
Contacts
Primary ContactMitchell Cairo, MD
Backup ContactLauren Harrison
Outcome results
None listed