A Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Kidney Transplant Recipients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03950414|
Recruitment Status : Recruiting
First Posted : May 15, 2019
Last Update Posted : October 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Cytomegalovirus Infections Kidney Transplant Infection||Biological: CMV specific T-cells||Phase 1|
Viral infections, or their reactivation in the immunocompromised host, remain serious complications that adversely affect outcomes of transplantation. These infections may be refractory to pharmacologic treatment and result in increased morbidity and mortality after transplantation. Furthermore, the available pharmacologic therapies can result in severe toxicities.
Once an infection occurs, adequate immune reconstitution is decisive for recovery from viral disease after kidney transplantation. The present trial will consist of the treatment of kidney transplant recipients diagnosed with severe CMV infection when standard antiviral therapy is ineffective (disease progression on therapy, decline in viral load less than 10-fold in 2 weeks, known drug resistance), or toxic (end-organ damage), with virus-specific T cells using the CliniMACS® Prodigy System. As described in the background section, these are the patients with the greatest unmet need and greatest risk or morbidity and allograft loss due to CMV infection. 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 primary objective of this Phase I trial is to evaluate the safety and tolerability of CMV-specific T-cell transfer in adult patients suffering from CMV infections following kidney transplantation using a dose escalation design. The incubation with viral antigens (MACS GMP PepTivator) allows the enrichment of CMV-specific CD4+(Cluster of Differentiation 4) and CD8+(Cluster of Differentiation 8) T cells. Increasing evidence of the safety and efficacy of CMV-specific T-cell is available. Furthermore, the safety and efficacy of the specific manufacturing approach using the fully automated protocol of the ClinMACS® Prodigy for the isolation of CMV-specific T cells against CMV has been described and demonstrated that these cells retain their biological properties.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||3+3 dose-escalation, open label, non-randomized, non-placebo controlled, single group assignment study|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Kidney Transplant Recipients|
|Actual Study Start Date :||September 27, 2019|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||August 2023|
Experimental: Tier 1
3 participants enrolled at dose level 5x10^3 cells/kg of CMV viral specific T-cells
Biological: CMV specific T-cells
Naturally occurring, allogeneic donor lymphocytes derived from a leukapheresis or a whole blood product, enriched for CMV-specific CD4+ and CD8+ T cells Suspension of CMV-specific T cells in 10 mL of 0.9% NaCl with 2% Human Serum Albumin(HSA) via IV bolus injection
- Safety and Tolerability:Time of Occurence of Acute GVHD [ Time Frame: up to 15 weeks ]Time to occurrence of acute GVHD of any grade will be evaluated using the Kaplan-Meier method to assess incidence and severity of acute 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. 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.
- Safety and Tolerability: Number of infusion-related adverse events [ Time Frame: up to 7 weeks ]Incidence of grades 3-5 infusion-related adverse events, grades 4-5 non-hematological adverse events within four weeks of the CMV-VST dose that are not due to the pre-existing infection or original malignancy or pre-existing co-morbidities
- Incidence of acute infusion-related toxicity [ Time Frame: from T-cell transfer to 4 hours post injection, upto 3 weeks ]Incidence of acute infusion-related toxicity as assessed by maximum toxicity on the day of T-cell transfer, evaluated by measuring vital signs prior to and at different times after the T-cell transfer and monitoring of specific adverse events (chills, nausea, vomiting, diarrhea, abdominal pain, allergic reactions, respiratory dysfunction or headache from T-cell transfer to 4 hours post injection)
- Severity of acute infusion-related toxicity as measured by Cytokine release syndrome (CRS) Grading criteria [ Time Frame: from T-cell transfer to 4 hours post injection, upto 3 weeks ]
Severity of acute infusion-related toxicity will be assessed by CRS grading criteria.
Grade 1 Symptoms are not life threatening and require symptomatic treatment only, (e.g., fever, nausea, fatigue, headache, myalgias, malaise) Grade 2 Symptoms require and respond to moderate intervention Grade 3 Symptoms require and respond to aggressive intervention Grade 4 Life-threatening symptoms Grade 5 Death
Any grade 3 or greater occurrence of CRS will be considered a serious adverse event for this study.
- Number of Participants of Newly Occurring Acute Rejection after T-cell Transfer [ Time Frame: up to 15 weeks ]Incidence and severity of acute rejection of the kidney allograft will in part be measured by number of participants of newly occurring acute rejection after T-cell transfer
- Incidence of de novo Antibodies against Kidney Allograft Donor (dnDSA) after T-cell Transfer [ Time Frame: up to 55 weeks ]Incidence and severity of acute rejection of the kidney allograft will in part be measured by presence of de novo antibodies against kidney allograft donor (dnDSA) after T-cell transfer
- Incidence of GVHD Grade ≥1 [ Time Frame: up to 15 weeks ]Incidence and severity of Graft-versus-host disease (GVHD) will be measured by occurrence of acute GVHD grade ≥1 or aggravation of pre-existing acute GVHD after T-cell transfer
- Feasibility: Was production of CMV Virus specific T lymphocyte (VST) from donors accomplished? [ Time Frame: up to 3 weeks ]
There is no minimum cell count required for the study as it can vary. Successful production of CMV Virus specific T lymphocyte (VST) from donors will be tracked by a Yes/No question.
Production of cell accomplished: yes/no
- Feasibility: Participant Drop-out rate [ Time Frame: up to 3 weeks ]Evaluation of feasibility of CMV specific T cell transfer in adult patients suffering from severe CMV infection following kidney transplantation in part will be measured by participant drop out rate
- Feasibility: Time from patient inclusion to administration of CMV-VST [ Time Frame: up to 21 days ]Evaluation of feasibility of CMV specific T cell transfer in adult patients suffering from severe CMV infection following kidney transplantation in part will be measured by the amount of time from patient inclusion to administration of CMV-VST
- Efficacy: Percentage of patients with ≥1 log decrease in CMV viral load [ Time Frame: up to 15 weeks ]Evaluation of efficacy of CMV-specific T-cell transfer in adult patients suffering from severe CMV infection following kidney transplantation in part will be measured in terms of percentage of patients with ≥1 log decrease in CMV viral load at Week 12
- Efficacy:Time to 1 log change in CMV viral load [ Time Frame: up to 15 weeks ]Evaluation of efficacy of CMV-specific T-cell transfer in adult patients suffering from severe CMV infection following kidney transplantation in part will be measured in terms of time to 1 log change in CMV viral load
- Efficacy:Number of Participants with CMV clearance [ Time Frame: up to 15 weeks ]Efficacy evaluation in part will be measured by number of participants with CMV clearance. Either negative polymerase chain reaction (PCR) or <250 copies/mL will be considered as CMV clearance.
- Efficacy: Time of clearance of CMV [ Time Frame: up to 55 weeks ]Efficacy evaluation in part will be measured by number of days to achieve CMV clearance. Either negative polymerase chain reaction [PCR] or <250 copies/mL)will be considered as CMV clearance.
- Efficacy: Number of participants having CMV reactivation [ Time Frame: up to 55 weeks ]Efficacy in part will be measured by number of participants with CMV reactivations following initial viral clearance
- Efficacy: Overall Survival of Participant [ Time Frame: up to 55 weeks ]Overall survival rate of participants will be measured by time from T-cell transfer to death, graft loss, or last follow-up throughout the study
- Efficacy:Number of Participants with Clinical response/resolution of symptoms of underlying viral infection [ Time Frame: up to 15 weeks ]Efficacy in part will be measured by number of patients with resolution of clinical symptoms of underlying CMV infection from Day 7 (Week 1) to Week 12 after T-cell transfer as compared to Day 0
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): NCT03950414
|Contact: Constance B Trantow, MS, CCRCemail@example.com|
|United States, Wisconsin|
|University of Wisconsin School of Medicine and Public Health||Recruiting|
|Madison, Wisconsin, United States, 53705|
|Contact: Christopher Roginski 608-263-4505 firstname.lastname@example.org|
|Principal Investigator: Arjang Djamali, MD, MS, FASN|
|Principal Investigator:||Arjang Djamali, MD, MS, FASN||University of Wisconsin, Madison|
|Study Director:||Jacques Galipeau, MD||University of Wisconsin, Madison|