Phase I/II clinical trial to assess the safety and biological efficacy of treatment with virus-specific, cytotoxic T-lymphocytes from partially matched third-party unrelated donors, in stem cell transplant patients with viral reactivation unresponsive to standard therapy (R3ACT trial)
In allogeneic stem cell transplant patients, with viral reactivation unresponsive to standard antiviral therapy, is therapeutic infusion of most closely HLA-matched, third party, donor-derived, virus-specific cytotoxic T-lymphocytes, safe and efficacious?
Western Sydney Local Health Districit
30 participants
Feb 11, 2013
Interventional
Conditions
Summary
To assess the safety and efficacy of providing partially HLA matched, third party donor-derived, EBV/CMV/adenovirus-specific cytotoxic t-cells, to allogeneic stem cell/marrow transplant patients who have developed post-transplant viral infections unresponsive to standard therapy. It is hypothesised that virus-specific t-cells infusions will improve or restore the virus-specific immunity of the transplant patient in a safe manner without precipitating graft versus host disease.
Eligibility
Inclusion Criteria25
- Recipients of myeloablative or non-myeloablative allogeneic transplantation for any indication.
- Viral reactivation or infection with CMV, Adv or EBV as determined by:
- A) CMV
- CMV detectable by antigen detection, PCR or culture in peripheral blood or tissue biopsy or by immunohistochemical staining on tissue biopsy specimen
- B) Adv
- Presence of Adv as detected by PCR, antigen detection or culture in body fluids including blood, stool, urine or nasopharyngeal secretions
- C) EBV
- 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
- Failure of standard therapy as defined by:
- A) CMV
- The continued presence of detectable CMV virus or antigen after at least 14 days of antiviral therapy with IV ganciclovir or foscarnet
- Recurrence of detectable CMV virus or antigen after at least 2 weeks of prior antiviral therapy
- B) Adv
- A rise or less than 50% reduction in viral load in blood or any site of disease as measured by PCR or any quantitative assay despite use of therapy as determined by the treating physician (standard therapy may include intravenous cidofovir within the limits of renal function)
- C) EBV
- Increase or less than 50% decrease in the size of EBV lymphoma or
- Increase or less than 50% decrease in the EBV viral load in peripheral blood despite use of appropriate therapy as determined by the treating physician which may include:
- Reduction in immunosuppression
- Rituximab 375mg/m2 up to 4 infusions
- 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
- 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.
- Grade II or greater graft versus host disease within 1 week prior to infusion.
- Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
- ECOG status 4
- Privately insured patients (dependent on site)
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Interventions
Treatment will consist of an initial infusion of 2 x 10^7/m^2 partially HLA-matched (minimum 1/6), third party, donor-derived, virus-specific (CMV, EBV, and/or adenovirus) cytotoxic T-lymphocytes. Up to 3 subsequent infusions (with an option of increased dose up to 5 x 10^7/m^2) may be repeated at fortnightly intervals, on the basis of persistent viral reactivation.
Locations(15)
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ACTRN12613000603718