EBV Associated Lymphoma
Conditions
Keywords
Adoptive immunotherapy, EBV, Systemic EBV-positive T-cell lymphoma of childhood
Brief summary
Single-patient trial aiming to provide immunological consolidation following allogeneic stem cell transplantation to a young adult patient suffering from a systemic EBV-positive lymphoma of childhood.
Detailed description
Following a presumed primary EBV infection, a 19 year old female patient rapidly suffered systemic inflammatory response, hemophagocytosis, multi-organ failure and evidence of EBV+ T-cell lymphoma. The patient was aggressively treated and responded to SMILE-based chemotherapy. Once complete response was ascertained by PET imaging, the patient underwent myeloablative HLA-matched unrelated allogeneic stem cell transplantation (cyclophosphamide 60mg/Kg, total body irradiation - 12Gy with anti-thymocyte globulin). The stem cell donor had a positive serology for EBV (IgG). The patient's EBV titer was weakly positive at the time of transplantation. A decision was made to offer consolidative treatment consisting of donor-derived ex vivo expanded EBV-reactive T cells following transplantation. A EBV-specific T-cell line was manufactured from a portion of the cryopreserved G-CSF mobilized peripheral graft after appropriate authorizations were obtained. The patient suffered a severe episode of intestinal graft-versus-host disease early following transplantation but received a first dose of EBV-reactive T cells (20x10e6 T cells/meter square of body surface area 5 months post-transplantation
Interventions
BIOLOGICALEBV-specific T cells
Consolidative cellular immunotherapy consisting of one (or up to 4) infusion of ex vivo expanded T cells
Sponsors
Ciusss de L'Est de l'Île de Montréal
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single patient
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
1. Capacity to provide informed consent 2. Age ≥ 18 3. Negative serum pregnancy test and use of effective contraception method.
Exclusion criteria
1. Administration within less than 28 days of T-cell depleting antibodies (ATG, OKT3, Campath) 2. Pregnancy 3. Any abnormal condition or laboratory result that is considered by the Principal Investigator capable of altering patient or study outcome. 4. Active uncontrolled GVHD (acute GVHD grade II-IV or progressive extensive chronic GVHD) at time of enrolment or infusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of a donor-derived EBV-specific T-cell line as assessed clinically by the lack of graft-versus-host host (GVHD). | 1 year | Evaluate the safety in terms of occurrence of graft-versus-host disease of a donor-derived allogeneic EBV-specific T-cell line generation and infusion in a patient suffering from a life-threatening EBV-related disease who received an allogeneic stem cell transplantation. Acute GVHD symptoms will be scored using MAGIC criteria using scores from 0 to IV, IV being the most severe involvement) on skin, liver and gastro-intestinal tract. Chronic GVHD symptoms will be score using the NIH consensus scale (0 to 3, 3 being the most severe) on the following organs skin, mouth, eyes, GI tract, liver, lungs, joints and fascia, and genital tract. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response | 1 year | Disease recurrence as assessed by imaging (PET scanning) |
| Immune reconstitution to EBV | 1 year | Measurement of viral titers (nucleic acid testing) and peripheral blood ELISpot measurements |
Countries
Canada
Outcome results
None listed