Study of Adoptive Immunotherapy With Donor-derived CMV-specific T Cells for Recipients of Allo-HSCT (CMV_TCR-001)
Haematological Malignancies, CMV Infection
About this trial
This is an interventional treatment trial for Haematological Malignancies focused on measuring Ex vivo gene therapy, T cell receptor transduction, Immunotherapy, Allogeneic Haematopoietic Stem Cell Transplantation, CMV
Eligibility Criteria
Patient Inclusion Criteria:
- Undergoing matched sibling allogeneic HSCT for an underlying haematological malignancy with a CMV seronegative donor
- Age ≥ 18 years and ≤ 65 years
- HLA-A*0201 positive
- CMV seropositive (CMV IgG detected) pre-transplant
Informed consent in writing and ability to co-operate with treatment and follow up.
- Prepared to undergo additional study procedures as per study schedule
- Patient has undergone counselling about risk
- Serologically negative for HIV 1&2, Hep B, Hep C and syphilis
- Female patients of child-bearing age must have a negative pregnancy test and agree to use reliable contraceptive methods for the duration of the therapy and for 6 months afterwards
- Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards
And to be assessed prior to CMV-specific T cell infusion (for confirmation prior to product release):
- Donor engraftment (neutrophils > 0.5x109/l).
- Single positive CMV PCR result (> 200 copies/ml)
Patient Exclusion Criteria:
- Pregnant or lactating women
- Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae
- HIV infection
And to be assessed prior to CMV-specific T cell infusion (for confirmation prior to product release):
- Active acute GVHD > Grade I
- Concurrent use of systemic corticosteroids
Organ dysfunction as measured by
- creatinine > 200 uM/l
- bilirubin > 50 uM/l
- ALT > 3x upper limit of normal
Sites / Locations
- University Hospitals Birmingham NHS Foundation Trust
- University Hospitals Bristol NHS Foundation Trust
- University College London Hospital
- Nottingham University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort 1 - 10^4 transduced cells/kg
Cohort 2 - 10^5 transduced cells/kg
Cohort 1a - 10^3 transduced cells/kg
The first 3 patients will receive a single infusion of bulk CMV-TCR transduced donor-derived T cells on first CMV reactivation post allogeneic HSCT, at a dose of 10^4 T cells/kg recipient weight
If no cases grade III-IV GVHD in Cohort 1 the remaining patients (N=7) each receive a single infusion of bulk CMV-TCR transduced donor-derived T cells on first CMV reactivation post allogeneic HSCT, at a dose of 10^5 T cells/kg recipient weight
If 1 case grade III-IV GVHD in Cohort 1, next three patients to be treated with a single infusion of bulk CMV-TCR transduced donor-derived T cells of 1 x 10^3 T cells/kg recipient weight