Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cytomegalovirus Infections Solid Organ Transplant | 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 solid organ transplantation. The present trial will consist of the treatment of solid organ 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. 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 solid organ 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 |
Allocation: | N/A |
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) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients |
Actual Study Start Date : | September 27, 2019 |
Estimated Primary Completion Date : | August 2023 |
Estimated Study Completion Date : | August 2023 |
Arm | Intervention/treatment |
---|---|
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
|
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.
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
Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Adult (age ≥ 18 and ≤75) patients suffering from CMV reactivation/infections following solid organ transplantation (e.g., liver, pancreas, lung, heart, and multi-solid organ)
AND ONE OF THE FOLLOWING CRITERIA:
Exclusion Criteria:
Donor Eligibility
Donor selection priority: The original donor will be the first choice as the source of T cells. If donation from the original donor is not possible (e.g. such as donor is unavailable or ineligible), then an alternative related donor will be selected, with preference for those who have full HLA matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci).
Contact: Constance B Trantow, MS, CCRC | 608-265-7814 | cbt@clinicaltrials.wisc.edu |
United States, Wisconsin | |
University of Wisconsin School of Medicine and Public Health | Recruiting |
Madison, Wisconsin, United States, 53705 | |
Contact: Christopher Roginski 608-263-4505 ccrogins@clinicaltrials.wisc.edu | |
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 |
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | April 15, 2019 | ||||||
First Posted Date ICMJE | May 15, 2019 | ||||||
Last Update Posted Date | May 17, 2021 | ||||||
Actual Study Start Date ICMJE | September 27, 2019 | ||||||
Estimated Primary Completion Date | August 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
|
||||||
Original Primary Outcome Measures ICMJE |
|
||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE |
|
||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | A Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients | ||||||
Official Title ICMJE | A Phase I Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients | ||||||
Brief Summary | This study measures the tolerability of viral-specific T cells against Cytomegalovirus (CMV) in adult solid organ transplant (SOT) recipients. Participants are expected to be on study for 52 +/- 3 weeks. | ||||||
Detailed Description |
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 solid organ transplantation. The present trial will consist of the treatment of solid organ 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. 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 solid organ 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 ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: N/A 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)Primary Purpose: Treatment |
||||||
Condition ICMJE |
|
||||||
Intervention ICMJE | 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
|
||||||
Study Arms ICMJE | Experimental: Tier 1
3 participants enrolled at dose level 5x10^3 cells/kg of CMV viral specific T-cells
Intervention: Biological: CMV specific T-cells
|
||||||
Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
20 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | August 2023 | ||||||
Estimated Primary Completion Date | August 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
Donor Eligibility Donor selection priority: The original donor will be the first choice as the source of T cells. If donation from the original donor is not possible (e.g. such as donor is unavailable or ineligible), then an alternative related donor will be selected, with preference for those who have full HLA matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci).
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
|
||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03950414 | ||||||
Other Study ID Numbers ICMJE | 2019-0060 PACT VST-C-002 ( Other Grant/Funding Number: GALIPEAU SMPH START UP-PACT SUPPORT ) Protocol Version 3/18/2021 ( Other Identifier: UW Madison ) |
||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Responsible Party | University of Wisconsin, Madison | ||||||
Study Sponsor ICMJE | University of Wisconsin, Madison | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
|
||||||
PRS Account | University of Wisconsin, Madison | ||||||
Verification Date | May 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |