Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.
18 Years
N/A
Both
CMV Reactivation, Allogeneic Stem Cell Transplantation, Autologous CMV Specific CD8+ T Cells
Trial Information
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.
Inclusion Criteria:
1. Patients must have received an allogeneic stem cell transplant from any donor, as
treatment for a haematological malignancy.
2. HLAA0201 positive at one allele
3. CMV seropositive
4. The patient must be willing and capable of donating lymphocytes for CMVspecific CD8+
T cell selection using apheresis techniques
5. The patient must be in complete remission with no evidence of circulating blasts or
other malignant cells
6. Patient must be fit to undergo leukapheresis
7. Patients must have signed an informed consent form before undergoing LP prior to
alloSCT
Indications for infusion of autologous CMV specific CD8+ Tcells:
- Therapeutic: CMV disease following allogeneic stem cell transplantation
- Preemptive: CMV reactivation (by CMV DNA PCR)
- autologous CMV specific CD8+ T-cells must be infused into the patient no later than
72 following CMV reactivation.
- Steroids should be withdrawn at least 1 week before the infusion of CMVspecific CD8+
T-cell
- Patients must have signed an informed consent form before the infusion of autologous
CMV specific CD8+ T-cells
Exclusion Criteria:
1. Patient CMV seronegative
2. No informed consent
3. Patient positive at the time of LP for one of the following infectious agents: HIV,
HBV, HCV,Syphilis, HTLV 1 and 2
4. Patient with circulating leukemic blasts at the time of LP
Exclusion criteria for infusion of autologous CMV specific CD8+ T cells:
Severe GvHD (grade IIII-V) requiring full dose immunosuppressive treatment
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response to adoptive transfer of autologous CMV-specific CD8+ T-cells
Outcome Description:
Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.
Outcome Time Frame:
Up to three years
Safety Issue:
Yes
Principal Investigator
Katy Rezvani, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Imperial College Healthcare NHS Trust
Authority:
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study ID:
JROHH0202
NCT ID:
NCT01326273
Start Date:
April 2011
Completion Date:
June 2014
Related Keywords:
- CMV Reactivation
- Allogeneic Stem Cell Transplantation
- Autologous CMV Specific CD8+ T Cells
- CMV
- cytomegalovirus
- autologous
- leukemia
- hematological malignancies
- stem cell transplantation
- CMV reactivation
- adoptive therapy
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