Trial of CMV Specific DLIs From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allo SCT
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 11/24/2016 |
| Start Date: | February 2011 |
| End Date: | February 2018 |
| Contact: | Gwynn Long, MD |
| Email: | gwynn.long@duke.edu |
| Phone: | (919) 668-7395 |
A Pilot Trial of CMV Specific Donor Lymphocyte Infusions From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation
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.
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.
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.
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.
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/Exclusion Criteria
1. Adult donors must be the same donor used for the non-myeloablative allogeneic
transplant and must be a related family member with a HLA 3-6/6 match with the
subject and must be capable of providing informed consent; Potential donors under the
age of 18 must have a 'single patient exemption' approved by the Institutional Review
Board (IRB) and the donor and a guardian must provide assent. The donor must be the
same donor used for the original allogeneic transplantation. Selection of donors will
be compliant with 21 CFR 1271.
2. Adult donors must be CMV seropositive prior to transplant by CMV immune screen or CMV
IgG positive.
3. Donors will complete the Adult Donor History Questionnaire and have all laboratory
studies included in the Donor Referral NTL Panel, CBC with auto or manual
differential, and a Chemistry Panel within 7 days of scheduled collection procedure.
Donors who were evaluated greater than 1 year prior for transplant collection will
also have a history and Physical Exam, CXR, and EKG completed. Donors must not have
any medical condition which would make apheresis more than a minimal risk, and should
have normal range laboratory findings. All abnormal laboratory findings will be
evaluated by the treating physician within the context of the entire donor assessment
process.
4. Females of childbearing potential should have a negative serum beta-HCG (human
chorionic gonadotropin) test within 1 week of beginning apheresis.
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