Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells
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|ClinicalTrials.gov Identifier: NCT03798301|
Recruitment Status : Recruiting
First Posted : January 9, 2019
Last Update Posted : January 20, 2021
The present trial will consist of the treatment of 20 pediatric and adult Hematopoietic Stem Cell Transplantation (HSCT) recipients or immunocompromised participants diagnosed with opportunistic Cytomegalovirus (CMV) infections with virus-specific, antigen-selected T-cells. CMV-specific T-cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior studies on transfer of CMV specific T-cells have been shown to be safe and efficacious in the treatment of CMV infections.
The main trial objective is to evaluate the feasibility and safety of CMV-specific T-cell transfer in adult and pediatric participants suffering from CMV infections or reactivation following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic therapy).
Participants will be followed for one year.
|Condition or disease||Intervention/treatment||Phase|
|CMV Infection Cytomegalovirus Infections CMV Viremia Opportunistic Infections||Biological: CMV-specific T-cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||single-center, open-label, single-arm, pilot study|
|Masking:||None (Open Label)|
|Official Title:||Treatment of CMV Infections With Viral-Specific T Cells Against CMV in Pediatric and Adult Immunocompromised Patients or Recipients of Allogeneic Stem Cell Transplantation|
|Actual Study Start Date :||February 6, 2020|
|Estimated Primary Completion Date :||September 2025|
|Estimated Study Completion Date :||September 2026|
Experimental: Treatment Arm
Suspension of CMV-specific T-cells in 10 mL of 0.9% NaCl with 2% HSA. Single dose max. 25,000 T cells/kg body weight (BW) of the recipient delivered via IV bolus injection.
Biological: CMV-specific T-cells
Naturally occurring, allogeneic donor lymphocytes derived from a leukapheresis or a whole blood product, enriched for CMVspecific CD4+ and CD8+ T-cells
- Feasibility: Number of Participants Who Drop-Out Before T-Cell Transfer [ Time Frame: up to 21 days from enrollement ]The feasibility of this intervention will in part be accomplished by measuring the number of dropped out participants before T-Cell Transfer.
- Feasibility: Number of Days from Participant Enrollment to Administration of CMV-VST [ Time Frame: up to 21 days from enrollment ]The feasibility of this intervention will in part be accomplished by measuring the amount of time from participant enrollment to administration of Cytomegalovirus-Viral Specific T-Cells (CMV-VST).
- Feasibility: Successful production of CMV-VST from donors [ Time Frame: up to 21 weeks from enrollment ]The feasibility of this intervention will be assessed by quantifying the number of successful productions of Cytomegalovirus-Viral Specific T-Cells (CMV-VST) on an intent to treat basis.
- Safety: Number of Subjects who experience infusion-related adverse events following CMV-VST infusion [ Time Frame: up to 4 hours after CMV-VST infusion ]Incidence assessed by monitoring vital signs and specific adverse events
- Safety: Number of Subjects who experience newly occurring acute GVHD grade 1 [ Time Frame: up to 12 weeks from CMV-VST infusion ]Incidence of subjects who experience newly occurring acute GVHD grade 1
- Safety: Number of subjects experiencing newly occurring acute GVHD grade ≥ 2 or experience aggravation of pre-existing acute GVHD [ Time Frame: up to 12 weeks from CMV-VST infusion ]Incidence of newly occurring acute GVHD grade ≥ 2 or increase in grade of pre-existing acute GVHD
- Safety: Number of subjects experiencing chronic GVHD [ Time Frame: up to 12 weeks from CMV-VST infusion ]Incidence of chronic GVHD
- The number of severe infusion-related adverse events or severe non-hematological adverse events [ Time Frame: up to 28 days from CMV-VST infusion ]Incidence of infusion-related adverse events ≥ grade 3 and non-hematological adverse events ≥ grade 4 after CMV-VST, which are not due to pre-existing infection or original malignancy or pre-existing condition
- Safety: Time to Occurrence of GVHD [ Time Frame: up to 12 weeks from CMV-VST infusion ]Time to occurrence of acute GVHD of any grade or to occurrence of chronic GVHD will be evaluated using the Kaplan-Meier method to assess incidence and severity of acute or chronic GVHD from day of T-cell transfer. The first day of GVHD onset at a certain grade will be used to calculate a cumulative incidence curve for that GVHD grade, acute or chronic. Overall cumulative incidence curves will be computed along with the 95% confidence intervals until Week 12 after T-cell transfer with death considered as a competing risk.
- Efficacy: Percentage of Participants with a ≥1 log decrease in CMV viral load [ Time Frame: up to 12 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by percentage of participants with a ≥1 log decrease in CMV viral load at Week 12.
- Efficacy: Time to ≥1 log change in viral load [ Time Frame: up to 12 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by time to ≥1 log change in viral load in days.
- Efficacy: Number of Participants with CMV Clearance [ Time Frame: up to 12 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by the number of patients with CMV clearance, defined as negative Polymerase Chain Reaction (PCR) from Day 7 to Week 12 after T-cell transfer.
- Efficacy: Time to CMV Clearance [ Time Frame: up to 12 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by the time to CMV clearance (defined as negative PCR) from Day 0 to first day of two subsequent negative CMV PCR studies.
- Efficacy: Number of Participants with Reduction or Clearance of Clinical Symptoms [ Time Frame: up to 12 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by the number of participants with reduction or clearance of clinical symptoms of underlying CMV infection from Day 7 to Week 12 after T-cell transfer as compared to Day 0.
- Efficacy: Number of CMV Reactivations Following Initial Viral Clearance [ Time Frame: up to 52 weeks from CMV-VST infusion ]Evaluation of efficacy will in part be measured by the number of CMV reactivations following initial viral clearance until Week 52.
- Efficacy: Overall Survival [ Time Frame: up to 52 weeks ]Evaluation of efficacy will in part be measured by the overall survival. Overall survival rate (OS): time from T-cell transfer (Day 0) to death or last follow-up throughout the study from Day 1 to Week 52.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03798301
|Contact: Cancer Connectemail@example.com|
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center||Recruiting|
|Madison, Wisconsin, United States, 53705|
|Contact: Jenny Weiland 608-890-8070 firstname.lastname@example.org|
|Principal Investigator: Inga Hofmann, MD|
|Principal Investigator:||Inga Hofmann, MD||University of Wisconsin, Madison|
|Study Director:||Jacques Galipeau, MD||University of Wisconsin, Madison|