Cytomegalovirus Infections
Conditions
Keywords
nonmyeloablative allogeneic stem cell transplantation, cytomegalovirus, donor lymphocyte infusions, cytotoxic T lymphocyte
Brief summary
Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell transplants, this virus is a major cause of morbidity and mortality. While pharmacologic agents exist to treat CMV disease, these medications have numerous side effects, the most serious of which is myelosuppression. The frequency of neutropenia ranges from 41% to 58% in stem cell transplant (SCT) patients treated with ganciclovir. Withdrawal of anti-CMV therapy due to these complications may result in recurrent disease. The restoration of cellular immunity to CMV is necessary in order to prevent viral reactivation, and the generation of cytotoxic T cells against CMV early antigens is perhaps the most important part of the host immune response to CMV. At day 40 post-transplant, for example, at least 65% of SCT patients are deficient in CD8+ T-cell responses to CMV. Previous studies have demonstrated a direct correlation between CMV infection in these patients and cytotoxic T lymphocyte (CTL) function, with patients who have defects in cellular immunity being at high risk for invasive CMV disease. The median time post-transplant for the development of CMV disease is 50 to 60 days, and CMV re-activation occurs in 70 to 80% of CMV sero-positive SCT recipients. Without anti-viral therapy as many as 50% of these patients will develop CMV disease.
Detailed description
This protocol will evaluate the safety of CMV specific T cell infusion following nonmyeloablative stem cell transplantation from 3-6/6 HLA matched donors as well as evaluate the efficacy of antigen specific T cell infusions in preventing CMV activation.
Interventions
BIOLOGICALCMV Specific T Cell donor lymphocyte infusion
Donor Lymphocyte Infusion (DLI)
Sponsors
Nelson Chao
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects who have undergone a non-myeloablative allogeneic transplant, using a 3-6/6 Human Leukocyte Antigen (HLA) matched related donor. 2. Subjects must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG or develop detectable disease by PCR in the post-transplant setting. 3. Performance status must be Karnofsky 50-100%. 4. Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure and prior to the first infusion. 5. ≤ Grade 1 acute graft versus host disease (GVHD) at time of the CMV specific T cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned donor cell infusion). The dosage level of immunosuppressive therapy at the time of infusion should be no greater than 20 mg of prednisone daily or mycophenolate 1000 mg tid daily or cyclosporine with a target level of 200 ng/ml or equivalent. 6. At the time of the CMV specific T cell infusion, the recipient must have adequate organ function as indicated by \< Grade 3 across all organ systems except for hematologic toxicity. 7. Subject must be at least 18 years of age.
Exclusion criteria
1. Pregnant or lactating women, 2. Subjects with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise compliance with this protocol. 3. Subjects who had histopathologically confirmed overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible. Donor Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of CMV Specific T cell infusion following Stem Cell Transplant | 2 years | Donor Lymphocyte Infusion (DLI) of CMV Specific T cell clones following nonmyeloablative allogeneic stem cell transplant for the prevention of CMV |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of CMV-specific T cell infusion in terms of response, progression free survival, and overall survival | 2 years | The efficacy and its effect on survivability will be assessed. |
| Evaluate the recovery of immune function post engraftment with this regimen. | 2 years | Blood samples will be collected for immune reconstitution studies, including assessing CMV specific responses, just prior to each cell infusion, and 3,6, 12 months post last infusion. |
Countries
United States
Outcome results
None listed