R3ACT Randomised (R3R): A study for people with untreated viral infections following allogeneic stem cell transplantation to see whether the combination of best available therapy and immune cells improves outcomesA randomised trial of most closely HLA-matched third-party donor-derived virus-specific cytotoxic T-lymphocytes in patients with untreated viral infection post-allogeneic stem cell transplantation to reduce number of days in hospital

Inclusion

• Recipients of HLA matched or mismatched peripheral blood, bone marrow or cord blood myeloablative or non-myeloablative allogeneic stem cell transplantation for any indication within 6 months of transplant
• Reactivation or infection with CMV (cytomegalovirus) or EBV (Epstein barr virus) or EBV associated PTLD (post-transplant lymphoproliferative disorder) within 180 days following allogeneic stem cell transplantation must be present as determined by:
o For CMV
- CMV detectable by antigen detection, PCR or culture in peripheral blood or tissue biopsy or by immunohistochemical staining on tissue biopsy specimen
o For EBV
- Elevated EBV detectable in peripheral blood by PCR (polymerase chain reaction) or
- Presence of documented EBV related PTLD diagnosed by tissue biopsy or
- Elevated EBV detectable in the blood by PCR and clinical or imaging findings consistent with EBV lymphoma
• Patients must satisfy criteria for initiation of treatment within 180 days following allogeneic stem cell transplantation
o For CMV
- Most recent PCR in peripheral blood greater than or equal to 1,000 international units/ml (IU/ml) (3 log10) OR
- Positive antigen detection, PCR or culture in tissue in association with clinical symptoms and/or signs consistent with CMV tissue infection
o For EBV
- At least one post-transplant PCR in peripheral blood within two weeks greater than or equal to 10,000 viral genome copies/ml or two post-transplant PCRs in peripheral blood greater than or equal to 5,000 viral genome copies/ml if separated by an interval of at least 72 hours with the most recent value higher than the previous value
- Positive antigen detection, PCR or culture in tissue in association with clinical symptoms and/or signs and/or tissue biopsy or flow cytometry consistent with EBV tissue infection or EBV associated post-transplant lymphoproliferative disease
• Patients must not have received more than 7 days of prior treatment dose pharmacological anti-viral therapy for treatment of CMV or EBV infection Treatment dose pharmacological therapy is defined as:
o For CMV
- IV (intravenous) ganciclovir or oral valganciclovir at treatment dose or foscarnet at full dose or high dose acyclovir or one of its derivatives or brincidofovir or letermovir or maribivir at treatment doses (doses of aciclovir of 800 mg bd or valaciclovir 1 g/day or famciclovir 250mg bd or below will not be considered treatment dose)
o For EBV infection or EBV associated PTLD
- One dose of rituximab or other anti-CD20 antibody 7 days treatment with cytotoxic chemotherapy
- adequate hepatic and renal function (< 3 x upper limit of normal for AST (SGOT), ALT (SGPT), < 2 x upper limit of normal for total bilirubin, serum creatinine) unless abnormalities are considered to be due to the infection/PTLD being treated

• ECOG status 0 to 3 or Lansky score 30-100