Late Complication From Kidney TransplantPhase 1TASKNCT02088931
Treg Adoptive Therapy for Subclinical Inflammation in Kidney Transplantation
A Phase 1 study testing Treg infusion in people with Late Complication From Kidney Transplant, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of this study is to test the safety of the experimental therapy of a single infusion of Regulatory T cells (Tregs). The investigators want to find out what effects, good or bad, Tregs will have on the kidney transplant patients. There are different types of T cells. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Late Complication From Kidney Transplant
- What is being tested?
- Treg infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to 31 Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Recipients of primary renal transplants age 18-65 years with no donor specific antibodies prior to transplantation
- Stable renal function (cGFR), no history of acute rejection and proteinuria less than 500 mg/24 hours.
- Maintenance immunosuppression consisting of tacrolimus and mycophenolate mofetil/mycophenolic acid with or without prednisone
- Protocol renal allograft biopsy at 6 months with findings of 5%-25% inflammation (Banff t0 or t1)without evidence of rejection (Banff t0 or t1<5%)
- Blood PCR for BK less than 1000 copies/ml, and urine less than 500,000 copies/ml
- History of positive EBV serology
- Current immunizations including TdAP, hepatitis B, pneumococcal and seasonal influenza vaccines
Who cannot join
- Recipients of 6-antigen HLA matched kidney transplants from living or deceased donors
- Subjects with history of prior kidney transplant
- History of transplant renal artery stenosis
- History of wound healing complication following transplant surgery
- Known hypersensitivity to tacrolimus, mycophenolate mofetil/mycophenolic acid, or everolimus
- Subjects with history of autoimmune disease
Show all 19Show fewer
- Hematocrit < 33%; leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL
- Any current active infection
- Serologic evidence of HIV-1 or HIV-2 infection
- Evidence of current hepatitis B as demonstrated by HBsAg or circulating hepatitis B genomes
- Serologic evidence of hepatitis C infection
- Detectable circulating CMV genomes or active infection or high risk for CMV (CMV seronegative recipient receiving a kidney from a CMV seropositive donor)
- Detectable circulating EBV genomes
- History of positive PPD skin test, which was untreated.
- Subjects who may potentially require live virus vaccines within the first 12 months of the study
- History of malignancy (including squamous cell carcinoma of the skin or cervix) except adequately treated basal cell carcinoma
- Any chronic illness or prior treatment which in the opinion of the investigator should preclude participation in the trial
- Pregnant or breastfeeding women, any female who is unwilling to use a reliable and effective form of contraception for 2 years after Treg dosing, and any male who is unwilling to use a reliable and effective form of contraception for 3 months after Treg dosing
- Tregs present in peripheral blood at less than 30/µL
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Pilot Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy in Renal Transplant Recipients
The purpose of this study is to test the safety of the experimental therapy of a single infusion of Regulatory T cells (Tregs). The investigators want to find out what effects, good or bad, Tregs will have on the kidney transplant patients.
There are different types of T cells. This study uses Regulatory T cells (Tregs), which are found in the blood and are part of the immune system that stops other immune cells from working. Tregs help to turn off the immune system after other immune cells have finished tackling outside infections, and Tregs keep the immune system in check so that the body does not attack itself. The researchers are hoping that, by giving an infusion of Tregs that the attack on the kidney can be stopped and kidney function will be stabilized. It is not known if the Treg experimental therapy can stop the inflammation in the kidney.
In this study, the researchers will take some of Tregs from the patient, multiply them in the laboratory, and then infuse them back into the patient. The procedure used to multiply Tregs is an experimental process performed in the laboratory. Similar procedures done with mice have been shown to reverse inflammation but it is not known whether the results will be the same in humans. This therapy has not yet been done in humans outside of a research study.
Read the detailed description
This is an open-label single dose pilot study in which 3 subjects with inflammation on their 6-month surveillance biopsy following renal transplantation will receive a single infusion of a target of 320 million cells ex vivo selected and expanded autologous polyclonal Tregs.
AAt the time of Treg infusion (day 0), the immnosuppression will remain unchanged and consists of tacrolimus and mycophenolate acid with or without steroids. On the follow up biopsy, 2 weeks after the Treg infusion, the inflammatory load will be assessed by computer assisted image analysis looking at thenumber of infiltrating cells per square mm as well as the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus will be discontinued. These patients will remain on everolimus and mycophenolic acid with or without prednisone through the end of the study and the follow up period. If on the 2-week follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%, no change will be made to the maintenance immunosuppressive regimen consisting of tacrolimus, mycophenolic acid with or without prednisone. immunosuppression. All prescribing physicians are enrolled in and will participate in the FDA Mycophenolate Risk Evaluation and Mitigation Strategy.
Subjects will be enrolled at 4-6 week intervals. The first subject will receive an infusion and will be observed for 3 weeks prior to treatment of the remaining subjects. The study team (IND sponsor, protocol chair, and medical monitor) and the members of the DSMB will review the safety data of the first subject prior to proceeding.
If no grade 3 or higher related adverse event is observed, subsequent subjects may be treated. Otherwise treatment will be suspended pending review.
- Conditions
- Late Complication From Kidney Transplant
- Being tested
- Treg infusion
- Keywords
- Tregs, Kidney transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treg infusionBiological
At the time of Treg infusion (day 0), maintenance immunosuppression will remain unchanged which consists of TAC, MPA and steroids. On follow-up biopsy 2 weeks after Treg infusion, the inflammatory load will be assessed by computer assisted image analysis looking at the number of infiltrating cells per square mm as well as the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus will be discontinued. These patients will remain on everolimus, mycophenolic acid and prednisone through the end of the study and the follow-up period. If on the 2-week follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%, no change will be made to the maintenance immunosuppressive regimen consisting of TAC, MPA and prednisone.
| Study group | Role | What they receive |
|---|---|---|
| Single infusion polyclonal Treg | Experimental | 3 subjects with inflammation on their 6-month surveillance biopsy following renal transplantation will receive a single infusion of a target of 320 million ex vivo selected and expanded autologous polyclonal Tregs.
After the therapy visit the patient will return for a total of nine (9) more visits for the main part of the study: 1 and 4 days after therapy, then once a week for 4 weeks, and then 3, 6, and 12 months after you get the therapy. Receives: Biological: Treg infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients with Adverse Events.
Participants will be assessed for adverse events on days 0-1 (Treg infusion) and on days 4,7,14,21,28,84,180, and 360 (1 year).
Measured: 1 year
Patient Survival
Patient survival at 1 year and 3 years post renal transplantation.
Measured: 3 years
Renal Allograft Survival
Renal allograft survival at 1 year and 3 years post renal transplantation.
Measured: 3 years
Renal Allograft Dysfunction
Incidence of renal allograft dysfunction during the 1 year follow-up period post Treg infusion.
Measured: 1 year
Secondary outcomes (2)
Presence of Intragraft Tregs in the Renal Allograft Biopsy
Treg infiltration will be measured in the renal allograft on the post infusion kidney biopsy to observe the persistence of deuterium-labeled Tregs within the allograft.
Measured: 2 weeks
Change in circulating Treg Cells
Percentage of circulating Treg cells detected using deuterium labeling in the allograft biopsy.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2014 (estimated)
- Study startMar 2014
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Late Complication From Kidney TransplantStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Flavio Vincenti, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02088931
- Sponsor's protocol ID
- UCSFTX412ST
- Acronym
- TASK
- Status last verified
- Jul 2022
- First submitted
- 13 Jan 2014
- Last updated
- 13 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. Natural history, risk factors, and impact of subclinical rejection in kidney transplantation. Transplantation. 2004 Jul 27;78(2):242-9. doi: 10.1097/01.tp.0000128167.60172.cc.
PubMed 15280685Kee TY, Chapman JR, O'Connell PJ, Fung CL, Allen RD, Kable K, Vitalone MJ, Nankivell BJ. Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation. 2006 Jul 15;82(1):36-42. doi: 10.1097/01.tp.0000225783.86950.c2.
PubMed 16861939Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
PubMed 18510923Tang Q, Bluestone JA, Kang SM. CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. J Mol Cell Biol. 2012 Feb;4(1):11-21. doi: 10.1093/jmcb/mjr047. Epub 2011 Dec 14.
PubMed 22170955
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy in Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT02088931
- Acronym / sponsor ID
- TASK / UCSFTX412ST
- Conditions
- Late Complication From Kidney Transplant
- Keywords
- Tregs, Kidney transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 17 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety of the experimental therapy of a single infusion of Regulatory T cells (Tregs). The investigators want to find out what effects, good or bad, Tregs will have on the kidney transplant patients.
There are different types of T cells. This study uses Regulatory T cells (Tregs), which are found in the blood and are part of the immune system that stops other immune cells from working. Tregs help to turn off the immune system after other immune cells have finished tackling outside infections, and Tregs keep the immune system in check so that the body does not attack itself. The researchers are hoping that, by giving an infusion of Tregs that the attack on the kidney can be stopped and kidney function will be stabilized. It is not known if the Treg experimental therapy can stop the inflammation in the kidney.
In this study, the researchers will take some of Tregs from the patient, multiply them in the laboratory, and then infuse them back into the patient. The procedure used to multiply Tregs is an experimental process performed in the laboratory. Similar procedures done with mice have been shown to reverse inflammation but it is not known whether the results will be the same in humans. This therapy has not yet been done in humans outside of a research study.
Detailed description
This is an open-label single dose pilot study in which 3 subjects with inflammation on their 6-month surveillance biopsy following renal transplantation will receive a single infusion of a target of 320 million cells ex vivo selected and expanded autologous polyclonal Tregs.
AAt the time of Treg infusion (day 0), the immnosuppression will remain unchanged and consists of tacrolimus and mycophenolate acid with or without steroids. On the follow up biopsy, 2 weeks after the Treg infusion, the inflammatory load will be assessed by computer assisted image analysis looking at thenumber of infiltrating cells per square mm as well as the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus will be discontinued. These patients will remain on everolimus and mycophenolic acid with or without prednisone through the end of the study and the follow up period. If on the 2-week follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%, no change will be made to the maintenance immunosuppressive regimen consisting of tacrolimus, mycophenolic acid with or without prednisone. immunosuppression. All prescribing physicians are enrolled in and will participate in the FDA Mycophenolate Risk Evaluation and Mitigation Strategy.
Subjects will be enrolled at 4-6 week intervals. The first subject will receive an infusion and will be observed for 3 weeks prior to treatment of the remaining subjects. The study team (IND sponsor, protocol chair, and medical monitor) and the members of the DSMB will review the safety data of the first subject prior to proceeding.
If no grade 3 or higher related adverse event is observed, subsequent subjects may be treated. Otherwise treatment will be suspended pending review.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single infusion polyclonal Treg | Experimental | Biological: Treg infusion3 subjects with inflammation on their 6-month surveillance biopsy following renal transplantation will receive a single infusion of a target of 320 million ex vivo selected and expanded autologous polyclonal Tregs. After the therapy visit the patient will return for a total of nine (9) more visits for the main part of the study: 1 and 4 days after therapy, then once a week for 4 weeks, and then 3, 6, and 12 months after you get the therapy. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Recipients of primary renal transplants age 18-65 years with no donor specific antibodies prior to transplantation
- Stable renal function (cGFR), no history of acute rejection and proteinuria less than 500 mg/24 hours.
- Maintenance immunosuppression consisting of tacrolimus and mycophenolate mofetil/mycophenolic acid with or without prednisone
- Protocol renal allograft biopsy at 6 months with findings of 5%-25% inflammation (Banff t0 or t1)without evidence of rejection (Banff t0 or t1<5%)
- Blood PCR for BK less than 1000 copies/ml, and urine less than 500,000 copies/ml
Key exclusion criteria (19 listed)
- Recipients of 6-antigen HLA matched kidney transplants from living or deceased donors
- Subjects with history of prior kidney transplant
- History of transplant renal artery stenosis
- History of wound healing complication following transplant surgery
- Known hypersensitivity to tacrolimus, mycophenolate mofetil/mycophenolic acid, or everolimus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treg infusionAt the time of Treg infusion (day 0), maintenance immunosuppression will remain unchanged which consists of TAC, MPA and steroids. On follow-up biopsy 2 weeks after Treg infusion, the inflammatory load will be assessed by computer assisted image analysis looking at the number of infiltrating cells per square mm as well as the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus will be discontinued. These patients will remain on everolimus, mycophenolic acid and prednisone through the end of the study and the follow-up period. If on the 2-week follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%, no change will be made to the maintenance immunosuppressive regimen consisting of TAC, MPA and prednisone. | Biological | Single infusion polyclonal Treg |
Primary outcome
Number of Patients with Adverse Events.
Time frame: 1 year
Participants will be assessed for adverse events on days 0-1 (Treg infusion) and on days 4,7,14,21,28,84,180, and 360 (1 year).
Patient Survival
Time frame: 3 years
Patient survival at 1 year and 3 years post renal transplantation.
Renal Allograft Survival
Time frame: 3 years
Renal allograft survival at 1 year and 3 years post renal transplantation.
Renal Allograft Dysfunction
Time frame: 1 year
Incidence of renal allograft dysfunction during the 1 year follow-up period post Treg infusion.
2 secondary outcomes
Presence of Intragraft Tregs in the Renal Allograft Biopsy
Time frame: 2 weeks
Change in circulating Treg Cells
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
- Results publication: PubMed 15280685Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. Natural history, risk factors, and impact of subclinical rejection in kidney transplantation. Transplantation. 2004 Jul 27;78(2):242-9. doi: 10.1097/01.tp.0000128167.60172.cc.
- Results publication: PubMed 16861939Kee TY, Chapman JR, O'Connell PJ, Fung CL, Allen RD, Kable K, Vitalone MJ, Nankivell BJ. Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation. 2006 Jul 15;82(1):36-42. doi: 10.1097/01.tp.0000225783.86950.c2.
- Results publication: PubMed 18510923Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
- Results publication: PubMed 22170955Tang Q, Bluestone JA, Kang SM. CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. J Mol Cell Biol. 2012 Feb;4(1):11-21. doi: 10.1093/jmcb/mjr047. Epub 2011 Dec 14.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio Vincenti, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treg infusion in people with Late Complication From Kidney Transplant, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients with Adverse Events. (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02088931, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2022.