A Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients

  • STATUS
    Recruiting
  • End date
    Aug 21, 2023
  • participants needed
    20
  • sponsor
    University of Wisconsin, Madison
Updated on 15 February 2022
pneumonia
hla-a
ganciclovir
kidney transplant
valganciclovir
cidofovir
foscarnet
colitis
viral therapy
dhpg
viremia
letermovir
ivig

Summary

This study measures the tolerability of viral-specific T cells against Cytomegalovirus (CMV) in adult solid organ transplant (SOT) recipients. Participants are expected to be on study for 52 +/- 3 weeks.

Description

Viral infections, or their reactivation in the immunocompromised host, remain serious complications that adversely affect outcomes of transplantation. These infections may be refractory to pharmacologic treatment and result in increased morbidity and mortality after transplantation. Furthermore, the available pharmacologic therapies can result in severe toxicities.

Once an infection occurs, adequate immune reconstitution is decisive for recovery from viral disease after solid organ transplantation. The present trial will consist of the treatment of solid organ transplant recipients diagnosed with severe CMV infection when standard antiviral therapy is ineffective (disease progression on therapy, decline in viral load less than 10-fold in 2 weeks, known drug resistance), or toxic (end-organ damage), with virus-specific T cells using the CliniMACS® Prodigy System. These are the patients with the greatest unmet need and greatest risk or morbidity and allograft loss due to CMV infection. CMV-specific T cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior studies on transfer of CMV-specific T cells have been shown to be safe and efficacious in the treatment of CMV infections.

The primary objective of this Phase I trial is to evaluate the safety and tolerability of CMV-specific T-cell transfer in adult patients suffering from CMV infections following solid organ transplantation using a dose escalation design. The incubation with viral antigens (MACS GMP PepTivator) allows the enrichment of CMV-specific CD4+(Cluster of Differentiation 4) and CD8+(Cluster of Differentiation 8) T cells. Increasing evidence of the safety and efficacy of CMV-specific T-cell is available. Furthermore, the safety and efficacy of the specific manufacturing approach using the fully automated protocol of the ClinMACS® Prodigy for the isolation of CMV-specific T cells against CMV has been described and demonstrated that these cells retain their biological properties.

Details
Condition Cytomegalovirus Infections, Solid Organ Transplant
Treatment CMV specific T-cells
Clinical Study IdentifierNCT03950414
SponsorUniversity of Wisconsin, Madison
Last Modified on15 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Adult (age ≥ 18 and ≤75) patients suffering from CMV reactivation/infections following solid organ transplantation (e.g., liver, pancreas, lung, heart, and multi-solid organ)
CMV reactivation/viremia defined as positive (>250 copies/mL) CMV qPCR(quantitative polymerase chain reaction) AND/OR
Presence of symptoms secondary to CMV infection or evidence of invasive CMV infection (e.g. pneumonitis, colitis)
AND ONE OF THE FOLLOWING CRITERIA
Absence of an improvement of viral load after ≥ 14 days of standard antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold), or
New, persistent and/or worsening CMV-related symptoms, signs and/or markers of end organ compromise while on anti-viral therapy with medications such as ganciclovir, acyclovir, valganciclovir, foscarnet, cidofovir, IVIG(Intravenous immunoglobulin), and/or letermovir, or
Have contraindications or experience adverse effects of anti-viral therapy with medications such as ganciclovir, acyclovir, valganciclovir, foscarnet, cidofovir, IVIG, and/or letermovir, or
Known resistance to the anti-viral medications ganciclovir, foscarnet and/or cidofovir based on molecular testing 2. Availability of eligible donor 3. Written informed consent given by patient

Exclusion Criteria

Patient with acute rejection of allograft at time of T-cell transfer
Patient receiving steroids (>0.5 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer
Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days
Patients with CMV retinitis
Concomitant enrollment in another clinical trial interfering with endpoints of this study
Any medical condition which could compromise participation in the study according to the investigator's assessment
Known HIV infection
Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control during study treatment Note: Women of childbearing potential must have a negative serum pregnancy test at study entry
Patients unwilling or unable to comply with the protocol or unable to give informed consent
Donor Eligibility
Donor selection priority: The original donor will be the first choice as the source of T
cells. If donation from the original organ donor is not possible (e.g., donor is
unavailable or ineligible), then an alternative related donor will be selected, with
preference for those who have full HLA matching in 6/6 loci over those with partial HLA
matching (≥ 2/6 HLA loci). See Appendix 1 for patient and donor screening procedures
≥ 18 years old
Available and capable of undergoing a single standard 2 blood volume leukapheresis or
donation of one unit of whole blood
If the original transplant donor is not eligible, then an eligible fully matched or
Donors must be CMV IgG seropositive
eligible partially matched family member will be used as the donor
Related donors must be at least partially HLA compatible, matching with recipient in
at least 2/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this)
Donor must provide written informed consent
Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator
Peptide Pools of CMV pp65 before undergoing leukapheresis
Donor must meet the criteria for donor selection defined in the UWHC Hematopoietic
Stem Cell Transplant Program SOP and FACT standards, which comply with 21 CFR 1271
subpart C
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