RecruitingPhase 1ACTRN12621000323820

Virus-specific T cell therapy for transplant recipients

Phase I open-label clinical trial of allogeneic multi-virus-specific T cells for the treatment of viral complications in transplant recipients

Sponsor

QIMR Berghofer Medical Research Institute

Enrollment

25 participants

Start Date

May 31, 2021

Study Type

Interventional

Conditions

recurrent or drug-resistant viral infection Viral reactivation BK polyomavirus Disease relating to cytomegalovirus

Summary

Infectious complications following solid organ transplantation remains a major concern for transplant recipients. It is now firmly established that a delay in mounting virus-specific immune responses following transplant is a critical factor in allowing virus reactivation and viral disease. In particular, a group of immune cells called ‘T cells’ is important in fighting viruses. In this project we are focussing on four common viruses that cause complications in transplant patients: Epstein–Barr virus, cytomegalovirus, BK polyomavirus and adenovirus. In this trial we will test a therapeutic T cell therapy for solid organ transplant patients who are experiencing virus reactivation or disease. The T cell therapy has been grown from healthy donors and is ready to be administered to the transplant patients. Patients will receive four intravenous infusions of T cells over a period of approximately 4 weeks, and will then be followed up for approximately 14 weeks. One aim of this trial is to see if this T cell therapy is safe for transplant patients. In addition, we would like to see if the proportion of virus-specific immune T cells increases from before the first treatment, to the end of treatment and the end of follow-up.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria4

Aged 18 years or above
Previously received a solid organ transplant (kidney, lung, heart, liver, or a combination of these)
Viral infection or virus-induced neoplasia due to CMV, EBV, BKV or AdV, which is proven or suspected to be refractory to standard of care, or where standard of care is relatively or absolutely contraindicated.
Availability of a suitable batch of IP

Exclusion Criteria5

Significant non-malignant disease, e.g. severe cardiac or respiratory dysfunction
Uncontrolled psychosis, substance dependence, or any other psychiatric condition that may compromise the ability to participate in this trial
Prior cancers except: cancers with no evidence of disease recurrence and clinical expectation of recurrence of <5%; successfully treated non-melanoma skin cancer; localised prostate cancer; or carcinoma in situ of the cervix; or virus-induced neoplasia as specified in inclusion criterion 3.
Women who are pregnant, lactating or unwilling to use adequate contraception
Any other medical condition that, in the view of the Clinical Investigator, would prohibit participation

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Interventions

The investigational product (IP) is ‘multi-virus-specific T cells TI1’, and consists of T cells targeting cytomegalovirus (CMV), Epstein–Barr virus (EBV), BK polyomavirus (BKV) and adenovirus (AdV). IP has previously been be generated in a good manufacturing practices (GMP) facility from the peripheral blood of healthy donors recruited via the Australian Bone Marrow Donor Registry. Batches of IP will be selected for participants based on human leukocyte antigen matching and virus specificity of the product. The safety of the IP in a therapeutic setting will be tested in 25 patients who have received a solid organ transplant (kidney, lung, heart, liver, or a combination of these). Participants will be recruited from Princess Alexandra Hospital, The Prince Charles Hospital, Royal Brisbane and Women’s Hospital and Royal Adelaide Hospital. Administration of the Investigational product will be reordered in the case report forms and records of use in the product accountability logs. Four intravenous infusions of 4 × 10e7 cells suspended in clinical grade saline per infusion will be given; the second infusion will be 2 weeks after infusion one, to allow time to detect any immediate safety issues, and then infusions three and four will be delivered at 1-week intervals. At the Clinical Investigator’s discretion, the batch of T cells may be changed after two infusions. The IP will be administered intravenously over 5–10 min by a qualified person (e.g. registered nurse or clinician). This will be followed by a saline flush, which will take an additional 5–10 min.