Autologous Cytomegalovirus (CMV) Specific CD8+ T Cells as Treatment for CMV Reactivation
The investigators will assess whether the infusion of autologous CMV-specific T-cells at the time of CMV reactivation posttransplant will prevent worsening of CMV virus reactivation posttransplant to a level that warrants therapy with antiviral drugs (objectively assessed by looking at CMV virus copy number).
Allogeneic Stem Cell Transplantation
Autologous CMV Specific CD8+ T Cells
Procedure: CMV specific lymphocyte infusion
Procedure: Peripheral blood for CMV DNA PCR
Procedure: Haematology/Blood chemistry
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.|
- Response to adoptive transfer of autologous CMV-specific CD8+ T-cells [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.
- The occurrence of subsequent CMV reactivations [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]The occurrence of subsequent CMV reactivations.
- Rate of complete response [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]The rate of complete response will be analyzed and compared to patients treated with anti-viral drugs only.
- Rate of early complete response [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]The rate of early complete response will be analyzed and compared to patients treated with anti-viral drugs only.
- Rate of subsequent CMV reactivation [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]The rate of subsequent CMV reactivation will be analyzed and compared to patients treated with anti-viral drugs only.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
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.