This trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus \[CMV\] specific cytotoxic T-lymphocytes \[CTLs\]) or allogeneic adenovirus-specific cytotoxic T lymphocytes (donor adenovirus-specific \[AdV\] specific CTLs) work in treating CMV or AdV reactivation or infection in participants who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill cancer cells in patients with cytomegalovirus or adenovirus that has come back after a stem cell or solid organ transplant.
PRIMARY OBJECTIVE I. Assess the safety and feasibility of administering virus specific-CTLs from haploidentical donors in transplant patients both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV/AdV infection despite standard therapy. OUTLINE:Patients are assigned to 1 of 2 Cohorts. COHORT A: Patients receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes intravenously (IV). Patients undergo blood, urine, saliva, cerebrospinal fluid (CSF), and bronchoalveolar fluid sample collection on the trial. COHORT B: Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV. Patients undergo blood, urine, saliva, CSF, and bronchoalveolar fluid sample collection on the trial. After completion of study treatment, participants are followed up at 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given intravenously
Given intravenously
Nationwide Children's Hospital
Columbus, Ohio, United States
RECRUITINGOhio State University Comprehensive Cancer Center
Columbus, Ohio, United States
SUSPENDEDIncidence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0
Measured as the proportion of patients with acute (a) graft versus host disease (GvHD) grades III-IV or graft rejection/failure within 30 days of the last dose of cytotoxic T-lymphocytes (CTLs) or grades 3-5 infusion-related adverse events within 7 days of the last does of CTLs or grades 4-5 non-hematological adverse events within 30 days of the last dose of CTLs and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities. Will be calculated by dividing by all evaluable patients and the corresponding 95% confidence intervals will be calculated.
Time frame: Up to 30 days post infusion
Feasibility defined as identifying a suitable donor within 4 weeks and meeting minimum T cell doses in the final product
Time frame: Up to 1 year
Antiviral activity defined as response to viral load
Complete response, partial response, stable disease or progression will be defined and proportion of each outcome will be calculated.
Time frame: At day 28
Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection
Time frame: Up to 1 year
Overall survival
Kaplan-Meier survival function will be used to estimate the survival probability.
Time frame: From last CTL infusion till death, assessed at 6 and 12 months
Risk for chronic GVHD
Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.
Time frame: At 6 and 12 months post CTL infusion
Systemic infections
Will be reported by etiologic agent, site of disease, date of onset, and severity.
Time frame: Within 6 months of CTL infusion
Secondary graft failure
Proportion of secondary graft failure for both populations will be assessed at 30 days post CTL infusion will be calculated and 95% confidence intervals will be estimated accordingly.
Time frame: 30 days post-CTL infusion
Effects of cytomegalovirus (CMV) specific-CTL on viral loads assessed by weekly reverse transcriptase-polymerase chain reaction
Time frame: Up to 1 year
Viral reactivations
Proportion of viral reactivations within 6 months will be calculated and 95% confidence intervals will be estimated accordingly.
Time frame: Up to 6 months
Clinical response to CTL infusions
Time frame: At 6 weeks and 3 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".
Time frame: Up to 1 year
The Ohio State University Comprehensive Cancer Center
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