Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.
Allogeneic Hematopoietic Stem Cell transplantation (allo-SCT) remains the only curative
approach for a number of patients with hematological malignancies. However, the use of
allo-SCT can expose patients to prolonged periods of immunosupression during which time
viral infections can be a significant cause of morbidity and mortality.
Human cytomegalovirus (CMV) infection and reactivation still represents one of the most
important and lifethreatening complications in immunocompromised patients. Prophylaxis or
early treatment with antiviral drugs after CMV reactivation have reduced the mortality
related to this complication. However, the antiviral drugs have many side-effects and are
costly. Furthermore, CMV infection refractory to antiviral treatment after alloSCT is
associated with a high mortality. A number of studies have shown the efficacy of selecting
Tcells against the virus from the donor and infusing them into the recipient (adoptive
transfer of immunity) to prevent or treat CMV reactivation. However this approach relies on
the donor having preexisitng immunity to CMV (50% of the healthy population is CMV
seronegative and therefore have no preexisting immunity against CMV). We propose an
alternative approach to collect CMV specific Tcells from the seropositive recipient prior to
transplantation; the autologous CMV specific T cells will then be infused back into the
recipient at the time of CMV reactivation post-transplant.
This approach is especially relevant where the donor is CMV seronegative or unavailable or
following the use of cord blood transplant where there is no memory T cell response to CMV.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response to adoptive transfer of autologous CMV-specific CD8+ T-cells
Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.
Up to three years
Katy Rezvani, MD
Imperial College Healthcare NHS Trust
United Kingdom: Medicines and Healthcare Products Regulatory Agency