Infusion of virus specific immune cells in patients at the first sign of virus infection after a blood or bone marrow transplant who have received less than 7 days of anti-viral treatment.

Phase 1

Completed

• Conditions: Cytomegalovirus reactivation or infection following allogeneic blood or marrow stem cell transplantation; Epstein Barr Virus reactivation or infection following allogeneic blood or marrow stem cell transplantation; Adenovirus reactivation or infection following allogeneic blood or marrow stem cell transplantation; Infection - Studies of infection and infectious agents; Blood - Haematological diseases

• Registration Number: ACTRN12618000343202
• Lead Sponsor: Western Sydney Local Health District

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-07
• Study Completion: 2020-09-24
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

1) Recipients of myeloablative or non-myeloablative allogeneic stem cell transplantation for any indication.
2) Reactivation or infection with cytomegalovirus (CMV), Adenovirus (Adv) or Epstein-Barr virus (EBV) or EBV associated post-transplant lymphoproliferative disease (PTLD) must be present at the time of infusion as determined by:
o For CMV
- CMV detectable by antigen detection, Polymerase chain reaction (PCR) or culture in peripheral blood or tissue biopsy or by immunohistochemical staining on tissue biopsy specimen within 7 days of trial inclusion
o For Adv
- AdV detectable by antigen detection, PCR or culture in body fluids including blood, stool, urine or nasopharyngeal secretions or by immunohistochemical staining on tissue biopsy specimen within 7 days of trial inclusion
o For EBV, any of the following within 7 days of trial inclusion
- Elevated EB virus detectable in peripheral blood by PCR or
- Presence of documented EBV related PTLD diagnosed by tissue biopsy or
- Elevated EB virus detectable in the blood by PCR and clinical or imaging findings consistent with EBV lymphoma
3) Patients must satisfy criteria for initiation of treatment
o For CMV
- Most recent PCR in peripheral blood greater than or equal to 1,000 viral genome copies/ml OR positive antigen detection, PCR or culture in tissue in association with clinical symptoms and/or signs consistent with CMV tissue infection
o For AdV
- For asymptomatic patients (ie no fever, diarrhoea, respiratory symptoms etc):
Most recent PCR in peripheral blood greater than or equal to 1000 viral genome copies/ml in blood OR 2 positive PCR tests in any organ system that was negative prior to transplant
- For symptomatic patients:
1 positive PCR test from a symptomatic organ or in blood OR 2 positive PCR tests in any organ system that was negative prior to transplant
o For EBV
- Most recent PCR in peripheral blood greater than or equal to 10,000 viral genome copies/ml OR positive antigen detection, PCR or culture in tissue in association with clinical symptoms and/or signs consistent with EBV tissue infection or EBV associated post-transplant lymphoproliferative disease
4) Patients must not have received more than 7 days of prior treatment dose pharmacological anti-viral therapy at the time of T cell infusion. Treatment dose pharmacological therapy is defined as:
o For CMV
- IV ganciclovir or foscarnet at full dose or high dose acyclovir or one of its derivatives or brincidofovir (doses of aciclovir of 800 mg bd or valaciclovir 1 g/day or below will not be considered treatment dose).
o For Adv
- cidofovir or brincidofovir
o For EBV
- rituximab
- cytotoxic chemotherapy
5) 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)
6) ECOG status 0 to 3 or Lansky score 30-100
7) Patient (or legal representative) has given informed consent.

Exclusion Criteria

1) Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion unless anti-lymphocyte globulin levels in blood shown to be below the lympholytic threshold prior to infusion.
2) Active grade II or greater graft versus host disease within 1 week prior to infusion.
3) Prednisone or methylprednisolone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
4) Dose of prednisone or methylprednisolone (if administered) not maintained at a stable level for 72 hours prior to T cell infusion
5) ECOG status 4 or Lansky score <30

Study & Design

• Study Type: Interventional
• Study Design: Not specified