Adenovirus, Primary Immune Deficiency Disorder
Conditions
Keywords
adenovirus, primary immune deficiency disorder, cytotoxic t-lymphocytes
Brief summary
Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in children, adolescents and young adults with refractory ADV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD
Interventions
adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.
Sponsors
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Johns Hopkins University
University of California, San Francisco
University of Colorado, Denver
Indiana University
Washington University School of Medicine
University of California, Los Angeles
New York Medical College
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All eligible patients will receive one dose of CTLs at the same dose. Patients who meet the criteria may need additional CTL doses up to 5 total.
Eligibility
Sex/Gender
ALL
Age
1 Months to 79 Years
Healthy volunteers
No
Inclusion 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 \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 12 weeks after each infusion | Patients will be followed for adverse events following each infusion of ADV CTLs |
| Incidence of Response to Treatment (Efficacy) | 12 weeks after last infusion | Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs |
Countries
United States
Contacts
Primary ContactMitchell Cairo, MD
Backup ContactLauren Harrison, RN
Outcome results
None listed