Cytomegalovirus Infections, Primary Immune Deficiency Disorder
Conditions
Keywords
Cytomegalovirus, CMV, cytotoxic t-lymphocytes
Brief summary
CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults (CAYA) with refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD
Interventions
DRUGviral specific cytotoxic t-lymphocytes
CMV specific CTLs will be collected from HLA matched or mismatched donors and manufactured in a GMP facility and administered to patients with refractory CMV infection.
Sponsors
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Johns Hopkins University
University of California, San Francisco
Washington University School of Medicine
Indiana University
Children's Hospital 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 be given CMV specific CTLs and dose is based on donor source: HLA matched and HLA mismatced
Eligibility
Sex/Gender
ALL
Age
1 Months to 79 Years
Healthy volunteers
No
Inclusion criteria
1\. Patients with refractory CMV infection post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with either * Increasing or persistent quantitative qRT-PCR DNA copies despite two weeks of appropriate anti-viral therapy AND/OR * Medical intolerance to anti-viral therapies including: * ANC \< 500/mm2 secondary to ganciclovir * 2 renal toxicity with foscarnet And/or * known resistance to ganciclovir and/or foscarnet 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 Donor Eligibility Related donor available with a T-cell response to the CMV MACS® GMP PepTivator antigen(s). a. Third Party 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 CMV and/or a T-cell response to the CMV MACS® GMP PepTivator . 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 CMV CTL infusion Patient receiving steroids (\>0.5 mg/kg prednisone equivalent) at the time of CMV CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CMV CTL infusion Thymoglobulin (ATG), Alemtuzumab or T cell immunosuppressive monoclonal antibodies within 30 days Patient with poor performance status determined by Karnofsky (patients \>16 years) or Lansky (patients ≤16 years) score ≤30% CMV retinitis Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory CMV 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 CMV retinitis, meningitis, encephalitis, and/or cerebritis
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 following the administration of CMV CTLs |
| Incidence of Response to Treatment | Patients will be followed 12 weeks after each infusion | Patients will be followed for improvement in viral infection by monitoring CMV PCR weekly for response to treatment with CTLs |
Countries
United States
Contacts
Primary ContactMitchell S Cairo, MD
Backup ContactLauren Harrison, RN
Outcome results
None listed