Clinical trial
A Phase I Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients
Name
2019-0060
Description
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.
Trial arms
Trial start
2019-09-27
Estimated PCD
2022-07-11
Trial end
2022-07-11
Status
Terminated
Phase
Early phase I
Treatment
CMV specific T-cells
Naturally occurring, allogeneic donor lymphocytes derived from a leukapheresis or a whole blood product, enriched for CMV-specific CD4+ and CD8+ T cells Suspension of CMV-specific T cells in 10 mL of 0.9% NaCl with 2% Human Serum Albumin(HSA) via IV bolus injection
* Low Dose Tier - Viral-Specific T cell infusion 5 x10\^3 cells/kg body weight(BW)
* Mid Dose Tier - Viral-Specific T cell infusion 1.25 x10\^4 cells/kg BW
* High Dose Tier - Viral-Specific T cell infusion 2.5 x10\^4 cells/kg BW Product will be administered fresh intravenously to recipient within four hours of collection.
Arms:
Tier 1
Size
2
Primary endpoint
Safety and Tolerability:Time of Occurence of Acute GVHD
up to 15 weeks
Safety and Tolerability: Number of infusion-related adverse events
up to 7 weeks
Incidence of acute infusion-related toxicity
from T-cell transfer to 4 hours post injection, upto 3 weeks
Severity of acute infusion-related toxicity as measured by Cytokine release syndrome (CRS) Grading criteria
from T-cell transfer to 4 hours post injection, upto 3 weeks
Number of Participants of Newly Occurring Acute Rejection after T-cell Transfer
up to 15 weeks
Incidence of de novo Antibodies against Organ Allograft Donor (dnDSA) after T-cell Transfer
up to 55 weeks
Incidence of GVHD Grade ≥1
up to 15 weeks
Eligibility criteria
Inclusion Criteria:
1. 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:
1. Patient with acute rejection of allograft at time of T-cell transfer
2. Patient receiving steroids (\>0.5 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer
3. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days
4. Patients with CMV retinitis
5. Concomitant enrollment in another clinical trial interfering with endpoints of this study
6. Any medical condition which could compromise participation in the study according to the investigator's assessment
7. Known HIV infection
8. 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.
9. 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.
1. ≥ 18 years old
2. Available and capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood.
3. If the original transplant donor is not eligible, then an eligible fully matched or eligible partially matched family member will be used as the donor.
4. 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).
5. Donors must be CMV IgG seropositive.
6. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator Peptide Pools of CMV pp65 before undergoing leukapheresis.
7. 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.
8. Donor must provide written informed consent.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '3+3 dose-escalation, open label, non-randomized, non-placebo controlled, single group assignment study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 2, 'type': 'ACTUAL'}}
Updated at
2024-02-20
1 organization
1 product
2 indications
Organization
University of Wisconsin, MadisonProduct
CMV specific T-cellsIndication
Cytomegalovirus InfectionsIndication
Organ Transplant