Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lymphopheresis | Procedure | Lymphopheresis | ||
| CMV specific lymphocyte infusion | Procedure | CMV specific lymphocyte infusion | ||
| Peripheral blood for CMV DNA PCR | Procedure | Peripheral blood for CMV DNA PCR | ||
| Haematology/Blood chemistry | Procedure | Haematology/Blood chemistry analysis, Collection of blood for ancillary laboratory tests. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The occurrence of subsequent CMV reactivations | The occurrence of subsequent CMV reactivations. | Up to three years |
| Rate of complete response | The rate of complete response will be analyzed and compared to patients treated with anti-viral drugs only. |
Not provided
Inclusion Criteria:
Indications for infusion of autologous CMV specific CD8+ Tcells:
Exclusion Criteria:
Exclusion criteria for infusion of autologous CMV specific CD8+ T cells:
Severe GvHD (grade IIII-V) requiring full dose immunosuppressive treatment
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Katy Rezvani, MD | Imperial College Healthcare NHS Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Hospital | London | W12 0HS | United Kingdom |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Up to three years |
| Rate of early complete response | The rate of early complete response will be analyzed and compared to patients treated with anti-viral drugs only. | Up to three years |
| Rate of subsequent CMV reactivation | The rate of subsequent CMV reactivation will be analyzed and compared to patients treated with anti-viral drugs only. | Up to three years |
| ID | Term |
|---|---|
| D007938 | Leukemia |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| D007937 | Leukapheresis |
| D001774 | Blood Chemical Analysis |
| ID | Term |
|---|---|
| D016238 | Cytapheresis |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D001781 | Blood Component Removal |
| D047589 | Leukocyte Reduction Procedures |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D008919 | Investigative Techniques |
| D019963 | Clinical Chemistry Tests |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided