Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation
- Conditions
- AdenovirusCytomegalovirus
- Interventions
- Device: CliniMACS
- Registration Number
- NCT05664126
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
The investigators want to learn if CMV- and ADV-specific T-cells (cells that fight infections) isolated (selected) from a donor using an automated medical device can be a safe treatment for treating patients with CMV, and ADV after transplant.This study will test the effects and safety of giving VSTs produced here at St. Jude in treating the participant's infection.
Primary objective
To determine the efficacy of VSTs to achieve a ≥1 log10 reduction in CMV and/or ADV viral load in the peripheral blood 4 weeks after VST infusion.
When the initial viral load is \<1 log10 above the threshold of detection, the objective is to achieve a reduction to below the threshold of detection.
Secondary objectives
* Determine the safety of VSTs when used to treat CMV and/or ADV viremia post-HCT.
* Determine the proportion of patients who achieve a negative viral load at 3 months post-infusion.
* Assess the persistence of response for 6 months post-infusion.
- Detailed Description
The study will have 2 cohorts. Cohort A will include haploidentical donor who is identical to the stem cell donor. Cohort B will include haploidentical donor who is different from the stem cell donor. Seropositive donors will be screened for the presence of CMV- and ADV-specific T-cells using a functional flow cytometry assay. The donor will be considered suitable if the percentage of CD3+/IFN-γ+ cells is greater than 0.01% of CD3+ T-cells. Donor leukocytes will be collected using the Spectra Optia system. CMV- and ADV-specific T-cells will be isolated from donor leukocytes by 'IFN-γ-capture' technology using the Prodigy device over a 24-36 hour period and infused.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort B CliniMACS Cohort B will include haploidentical donor who is different from the stem cell donor Cohort A VST infusion Cohort A will include haploidentical donor who is identical to the stem cell donor. The first 5 patients will be enrolled in Cohort A. If safety criteria are met, cohort B will be open for enrollment. Cohort A CliniMACS Cohort A will include haploidentical donor who is identical to the stem cell donor. The first 5 patients will be enrolled in Cohort A. If safety criteria are met, cohort B will be open for enrollment. Cohort B VST infusion Cohort B will include haploidentical donor who is different from the stem cell donor
- Primary Outcome Measures
Name Time Method Degree of reduction of CMV and/or ADV viral load 4 weeks after VST infusion The primary objective of this clinical study is to evaluate the efficacy of adoptively transferred CMV- and ADV-specific haploidentical T-cells in patients who have undergone allogeneic HCT. This primary endpoint is defined as ≥1 log10 reduction in CMV and/or ADV viral load 4 weeks after VST infusion. When the initial viral load is \<1 log10 above the threshold of detection the endpoint will be a reduction to below the threshold of detection. The success rate will be evaluated using descriptive statistics (sample proportion and standard error). Patients with both CMV and ADC detected will count as success if reduction occurs in one or both of CMV and ADV.
- Secondary Outcome Measures
Name Time Method Incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy 4 weeks after VST infusion The incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Incidence of infusion-related grade 3-5 adverse events 24 hours after infusion 24 hours after infusion The incidence of infusion-related grade 3-5 adverse events will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Incidence of Grade 3-4 Neurotoxicity of any duration 4 weeks after VST infusion The incidence of Grade 3-4 Neurotoxicity of any duration will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Incidence of Grade 3-4 GVHD 4 weeks after VST infusion The incidence of Grade 3-4 GVHD will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Incidence of secondary graft failure attributable to VST 4 weeks after VST infusion The incidence of secondary graft failure attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Persistence of response at 6 months post-infusion 6 months after VST infusion The persistence of response at 6 months post-infusion will be assessed using descriptive statistics (sample proportions with standard errors)
Incidence of grade 3-5 non hematologic toxicities attributable to VST 4 weeks after VST infusion The incidence of grade 3-5 non hematologic toxicities attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)
Proportion of patients who achieve a negative viral load result at 3 months 3 months after VST infusion The proportion of patients who achieve a negative viral load result at 3 months will be assessed using descriptive statistics (sample proportions with standard errors)
Trial Locations
- Locations (1)
St . Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States