Cytomegalovirus (CMV) Specific Cytotoxic T Lymphocytes (CTL) When Used for Prophylaxis Against CMV in Recipients of Allogeneic, T Cell Depleted Stem Cell Transplants
| Status: | Completed |
|---|---|
| Conditions: | Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 2 - 65 |
| Updated: | 6/29/2017 |
| Start Date: | October 2007 |
| End Date: | August 6, 2008 |
A Phase I-II Randomized Trial to Examine the Clinical, Immunologic and Virologic Effects of CMV Specific CTL When Used for Prophylaxis Against CMV Disease in Recipients of Allogeneic, T Cell Depleted Stem Cell Transplants
This study examines the immunologic and virologic effects of prophylactic CMV specific CTL
in recipients of T cell depleted stem cell transplant (TCD SCT) at Duke University Medical
Center (DUMC), by measuring levels of CMV DNA and virus specific T cell precursors at
intervals post-infusion.
in recipients of T cell depleted stem cell transplant (TCD SCT) at Duke University Medical
Center (DUMC), by measuring levels of CMV DNA and virus specific T cell precursors at
intervals post-infusion.
Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in
immunocompromised individuals, such as recipients of stem cell or organ 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. Considering the risk associated with persistent infection and the
potential for CMV specific CTL to restore immunity, we propose to study the immunologic and
virologic effects of CMV pp65 specific CTL given to SCT recipients prophylactically, levels
of CMV pp65 specific CTL and CMV DNA will be measured from CTL recipients and a control
group randomized to not receive CTL.
All treatments will be given at Duke University Medical Center (DUMC).
1. Patients will have a complete set of vital signs and physical examination prior to each
infusion. Pulse oximetry will be monitored prior to, during, and for 30 minutes after
the T-cell infusion. Thirty minutes prior to the CTL infusion, patients will be
pre-medicated with 15 mg/kg (maximum 1 g) of acetaminophen p.o. and 1.0 mg/kg
diphenhydramine I.V. (maximum 50 mg). Cells will be thawed in the Cell Therapy lab at
DUMC, an aliquot sent for gram stain and culture, and viability will be determined.
Cells with > 70 % viability will be transferred to the clinical unit and infused over
5-10 minutes.
2. CMV CTL will be infused when available between days 30 and 40 post-transplant at a dose
ranging from 2- 5 x 105 cells/kg. This dose range was established since there may be
variability in the numbers of CTL expanded from these donors.
immunocompromised individuals, such as recipients of stem cell or organ 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. Considering the risk associated with persistent infection and the
potential for CMV specific CTL to restore immunity, we propose to study the immunologic and
virologic effects of CMV pp65 specific CTL given to SCT recipients prophylactically, levels
of CMV pp65 specific CTL and CMV DNA will be measured from CTL recipients and a control
group randomized to not receive CTL.
All treatments will be given at Duke University Medical Center (DUMC).
1. Patients will have a complete set of vital signs and physical examination prior to each
infusion. Pulse oximetry will be monitored prior to, during, and for 30 minutes after
the T-cell infusion. Thirty minutes prior to the CTL infusion, patients will be
pre-medicated with 15 mg/kg (maximum 1 g) of acetaminophen p.o. and 1.0 mg/kg
diphenhydramine I.V. (maximum 50 mg). Cells will be thawed in the Cell Therapy lab at
DUMC, an aliquot sent for gram stain and culture, and viability will be determined.
Cells with > 70 % viability will be transferred to the clinical unit and infused over
5-10 minutes.
2. CMV CTL will be infused when available between days 30 and 40 post-transplant at a dose
ranging from 2- 5 x 105 cells/kg. This dose range was established since there may be
variability in the numbers of CTL expanded from these donors.
Inclusion Criteria:
- Any allogeneic stem cell transplant recipient > 2 years of age who is CMV
sero-positive and has a CMV sero-positive donor,
- Bilirubin < 2.0 mg/dl; SGOT/SGPT < 2.5 X normal.
- Creatinine clearance > 50 cc/min as estimated by patient's serum creatinine, weight,
and age.
- Pulse oximetry > 95% on no supplemental oxygen.
- ECOG performance status < 2; for patients, 16 years of age, Lansky performance status
>70%.
Exclusion Criteria:
- Sero-negative patients with a history of GVHD of grade II or greater by the
Glucksberg crireria (protocol Appendix I) at or prior to day +30 of current stem cell
transplant are excluded.
- Patients who have received a prior stem cell transplant are excluded.
- Patients who are moribund or who because of cardiac, pulmonary, renal, hepatic or
neurologic dysfunction are not expected to survive one month.
- Subjects receiving systemic immunosuppressive agents for the treatment of GVHD at the
time of the CTL infusion will be excluded from receiving CTL, and subjects randomized
to not receive CTL will also be removed from study if at the time of the CTL infusion
they require systemic immunosuppression for treatment of GVHD
- Donors must be negative for HIV-1, HIV-2, and HTLV-2, and have passed all screening
tests for hepatitis.
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