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.
Therapeutic infusion of most closely HLA-matched third party donor-derived virus-specific cytotoxic T-lymphocytes in patients with previously untreated viral infection post-allogeneic stem cell transplantation
Western Sydney Local Health District
31 participants
Aug 9, 2017
Interventional
Conditions
Summary
This project aims to determine whether infusing virus specific T cells from normal donors and frozen in liquid nitrogen is safe and effective therapy in patients at the first sign of virus infection after blood or bone marrow transplant. During the project a bank of frozen virus specific T cells will be created and if a blood or marrow transplant patient develops a virus infection that needs treatment, cells from the bank will be used early during the infection to see if they can recreate immunity to the infection and avoid the necessity for prolonged used of toxic antiviral drugs.
Eligibility
Inclusion Criteria31
- Recipients of myeloablative or non-myeloablative allogeneic stem cell transplantation for any indication.
- 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
- 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:
- 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
- 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
- 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)
- ECOG status 0 to 3 or Lansky score 30-100
- Patient (or legal representative) has given informed consent.
Exclusion Criteria5
- 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.
- Active grade II or greater graft versus host disease within 1 week prior to infusion.
- Prednisone or methylprednisolone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
- Dose of prednisone or methylprednisolone (if administered) not maintained at a stable level for 72 hours prior to T cell infusion
- ECOG status 4 or Lansky score <30
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Interventions
Up to four doses of (2 x 10^7/m2) most closely HLA matched virus-specific cytotoxic T-Lymphocytes (CTL's), given via intravenous infusion, in patients with active viral replication (cytomegalovirus[CMV], adenovirus or Epstein Barr Virus [EBV]) post allogeneic haematopoietic stem cell transplant no less than 28 days apart. Following the first infusion, patients will be eligible for up to 3 additional CTL infusions (total maximum four infusions) with a minimum of 28 days between each infusion if at the time of subsequent infusion they are not showing at least a partial virological response to the previous infusion (defined as at least 50% reduction in viral copy number in blood compared with the copy number before the previous infusion) or if there is evidence of ongoing tissue infection or EBV lymphoma that has not shown clinical or radiological improvement since the previous infusion. Patients will continue to be eligible subsequent infusions if they have adequate hepatic and renal function (<3 x ULN for AST, ALT, <2 x ULN for bilirubin and serum creatinine), neutrophil count > 1x10^9 without G-CSF support for 3 days. The patient must not have had anti-lymphocyte globulin 4 weeks prior to the infusion or planned 4 weeks after the infusion, grade II or greater GVHD within 1 week prior to the infusion or prednisone/methylprednisone >1mg/kg administered within 72 hours prior to the cell infusion. The infusions will occur in the hospital outpatient unit where the patient will be observed for 2 hours after the infusion by nursing staff. The infusion will be administered in accordance with BMT policy and procedure by qualified staff such as the treating physician, fellow or nurse practitioner.
Locations(3)
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ACTRN12618000343202