Chronic Graft vs Host DiseasePhase 1GVHD-TReGNCT03683498
Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-host-Disease
A Phase 1 study testing Regulatory T-cell enriched infusion in people with Chronic Graft vs Host Disease, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
Trial summary
A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Chronic Graft vs Host Disease
- What is being tested?
- Regulatory T-cell enriched infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSpain
- Study dates
- 25 Sep 2018to 24 Mar 2022
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Recipient of allogeneic hematopoietic stem cell transplantation.
- Participants must have steroid-refractory cGVHD and had obtained a partial response after at least 4 weeks of treatment with ruxolitinib.
- Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) despite the use of prednisone at ≥0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms.
- Stable dose of glucocorticoids for 4 weeks prior to enrolment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
- No age limit. In the case of children participating in the study, the informed consent will be signed by a parents or legal guardians
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Participants must have adequate organ function
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Ongoing prednisone requirement >1 mg/kg/day (or equivalent).
- Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
- History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
- New immunosuppressive medication in the 4 weeks prior.
- Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior.
- Post-transplant exposure to T-cell or Interleukin-2 targeted medication (e.g. alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
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- Donor lymphocyte infusion within 100 days prior.
- Active malignant relapse.
- Active uncontrolled infection.
- Organ transplant (allograft) recipient.
- HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic hematopoietic stem cell transplant (HSCT). In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after hematopoietic stem cell transplant (HSCT).
- Other investigational drugs within 4 weeks prior to enrolment, unless cleared by the Principal Investigator.
- Pregnant women are excluded from this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in Patients Who do Not Obtain Complete Remission With Ruxolitinib
A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib
Read the detailed description
The study design is based on a phase I trial in Spanish.
A number of 16 patients will be included to assess the safety and maximum tolerated dose-level of donor regulatory enriched T cell (Treg) in steroid-refractory chronic graft versus host disease (cGVHD) patients who did not obtain complete remission under treatment with ruxolitinib.
- Conditions
- Chronic Graft vs Host Disease
- Being tested
- Regulatory T-cell enriched infusion
- Keywords
- Ruxolitinib, T cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regulatory T-cell enriched infusionBiological
Enrichment of CD25hi regulatory T cells from CD8 and/or CD19 pre-depleted leukapheresis products.
| Study group | Role | What they receive |
|---|---|---|
| Regulatory T-cell enriched infusion | Experimental | Dose escalation sequential cohorts Regulatory T-cell enriched infusion (Cells/kg) will be administered. The cohorts will be dose escalated per the schema below:
Dose-level A: 0.5 x 10ˆ6 Cells/kg Dose-level B: 1 x 10ˆ6 cell/kg Dose-level C: 2 x 10ˆ6 cell/kg Receives: Biological: Regulatory T-cell enriched infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity and maximum tolerated dose
To determine the maximum tolerated dose (MTD) and toxicity of Treg-enriched infusion among patients receiving ruxolitinib.
Measured: Up 12 weeks after infusion
Secondary outcomes (7)
Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level.
Percentage of cells viability, negative gram stain/endotoxin, percentage of CD4+CD25+ cells and CD4+CD25+CD127- Treg in order to consider for the infusion.
Measured: Before 24 hours to infusion up infusion day
Clinical response of Treg-enriched infusion
Each participant should be assigned one of the following categories: 1) complete cGVHD response per NIH criteria, 2) partial cGVHD response per NIH criteria, 3) non-response (includes stable disease) per NIH criteria, 4) progressive cGVHD per NIH criteria, 5) malignant disease relapse, or 6) unknown (not assessable, insufficient data).
Measured: Up 12 weeks after Treg infusion
Immunologic effects through phenotypical evaluation
Phenotypical evaluation of T cell populations (CD4, CD8, Treg), B and NK cells nuclear cells of Treg-enriched infusion among patients receiving ruxolitinib.
Measured: Up 12 weeks after Treg infusion
Immunologic effects through immune globulins.
Quantitative immune globulins of Treg-enriched infusion among patients receiving ruxolitinib
Measured: Up 12 weeks after Treg infusion
Immunologic effects through plasma banking
Plasma banking of Treg-enriched infusion among patients receiving ruxolitinib
Measured: Up 12 weeks after Treg infusion
Immunologic effects through additional mononuclear cells.
Storage of additional mononuclear cells of Treg-enriched infusion among patients receiving ruxolitinib
Measured: Up 12 weeks after Treg infusion
Survival after one year of Treg infusion
Number of patients alive after one year of Treg infusion
Measured: 1 year after Treg infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2018
- Study start25 Sep 2018
- Primary completion24 Mar 2022
- Study completion24 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft vs Host DiseaseStudies of the same condition, open and under way.
- 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
- Sequential
- Model description
- Initial enrollment will be at Dose-level A. Subsequent cohorts will be dose escalated.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- José Antonio Pérez-Simón, M.D. Ph.D., Principal investigator, Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03683498
- Sponsor's protocol ID
- GVHD-TReG
- Acronym
- GVHD-TReG
- Status last verified
- May 2022
- First submitted
- 18 Sep 2018
- Last updated
- 23 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Soares MVD, Gomez VE, Azevedo RI, Pereira PNG, Velazquez TC, Mendes L, Alho AC, Garcia-Guerrero E, Garcia-Calderon CB, Tharmaratnam K, Cabral IA, Ribeiro AC, Juncal C, Roncon S, Pais AT, Gil AR, Espada E, Rodrigues A, Garcao A, Yaspo ML, Warnatz HJ, Lehrach H, Ward L, Barbosa-Morais NL, Quintas AM, Palmela P, Caldas C, Ferreira R, Leite L, Martins C, Lourenco F, Moreno R, Campilho F, Cheyne CP, Garcia-Finana M, Campos A, Baron F, Arpinati M, Hoffmann P, Edinger M, Koreth J, Ritz J, Vaz CP, Perez-Simon JA, Lacerda JF. Phase 1/2 trials of donor regulatory T cells for the treatment of steroid-refractory chronic graft-versus-host disease. Blood Adv. 2026 May 12;10(9):2904-2915. doi: 10.1182/bloodadvances.2025017996.
PubMed 41637631
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in Patients Who do Not Obtain Complete Remission With Ruxolitinib
- ClinicalTrials.gov ID
- NCT03683498
- Acronym / sponsor ID
- GVHD-TReG / GVHD-TReG
- Conditions
- Chronic Graft vs Host Disease
- Keywords
- Ruxolitinib, T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 25 Sep 2018 (actual)
- Primary completion
- 24 Mar 2022 (actual)
- Study completion
- 24 Mar 2022 (actual)
- First posted
- 25 Sep 2018 (actual)
- 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.
A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib
Detailed description
The study design is based on a phase I trial in Spanish.
A number of 16 patients will be included to assess the safety and maximum tolerated dose-level of donor regulatory enriched T cell (Treg) in steroid-refractory chronic graft versus host disease (cGVHD) patients who did not obtain complete remission under treatment with ruxolitinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Initial enrollment will be at Dose-level A. Subsequent cohorts will be dose escalated.
| Arm | Type | Receives |
|---|---|---|
| Regulatory T-cell enriched infusion | Experimental | Biological: Regulatory T-cell enriched infusionDose escalation sequential cohorts Regulatory T-cell enriched infusion (Cells/kg) will be administered. The cohorts will be dose escalated per the schema below: Dose-level A: 0.5 x 10ˆ6 Cells/kg Dose-level B: 1 x 10ˆ6 cell/kg Dose-level C: 2 x 10ˆ6 cell/kg |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Recipient of allogeneic hematopoietic stem cell transplantation.
- Participants must have steroid-refractory cGVHD and had obtained a partial response after at least 4 weeks of treatment with ruxolitinib.
- Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) despite the use of prednisone at ≥0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms.
- Stable dose of glucocorticoids for 4 weeks prior to enrolment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
Key exclusion criteria (14 listed)
- Ongoing prednisone requirement >1 mg/kg/day (or equivalent).
- Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
- History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
- New immunosuppressive medication in the 4 weeks prior.
- Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior.
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 |
|---|---|---|
| Regulatory T-cell enriched infusionEnrichment of CD25hi regulatory T cells from CD8 and/or CD19 pre-depleted leukapheresis products. | Biological | Regulatory T-cell enriched infusion |
Primary outcome
Toxicity and maximum tolerated dose
Time frame: Up 12 weeks after infusion
To determine the maximum tolerated dose (MTD) and toxicity of Treg-enriched infusion among patients receiving ruxolitinib.
7 secondary outcomes
Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level.
Time frame: Before 24 hours to infusion up infusion day
Clinical response of Treg-enriched infusion
Time frame: Up 12 weeks after Treg infusion
Immunologic effects through phenotypical evaluation
Time frame: Up 12 weeks after Treg infusion
Immunologic effects through immune globulins.
Time frame: Up 12 weeks after Treg infusion
Immunologic effects through plasma banking
Time frame: Up 12 weeks after Treg infusion
Immunologic effects through additional mononuclear cells.
Time frame: Up 12 weeks after Treg infusion
Survival after one year of Treg infusion
Time frame: 1 year after Treg infusion
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 23 May 2022.
- Derived from this study: PubMed 41637631Soares MVD, Gomez VE, Azevedo RI, Pereira PNG, Velazquez TC, Mendes L, Alho AC, Garcia-Guerrero E, Garcia-Calderon CB, Tharmaratnam K, Cabral IA, Ribeiro AC, Juncal C, Roncon S, Pais AT, Gil AR, Espada E, Rodrigues A, Garcao A, Yaspo ML, Warnatz HJ, Lehrach H, Ward L, Barbosa-Morais NL, Quintas AM, Palmela P, Caldas C, Ferreira R, Leite L, Martins C, Lourenco F, Moreno R, Campilho F, Cheyne CP, Garcia-Finana M, Campos A, Baron F, Arpinati M, Hoffmann P, Edinger M, Koreth J, Ritz J, Vaz CP, Perez-Simon JA, Lacerda JF. Phase 1/2 trials of donor regulatory T cells for the treatment of steroid-refractory chronic graft-versus-host disease. Blood Adv. 2026 May 12;10(9):2904-2915. doi: 10.1182/bloodadvances.2025017996.
- Individual participant dataSharing planned: Undecided
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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.
José Antonio Pérez-Simón, M.D. Ph.D. principal investigator
Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.
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 Regulatory T-cell enriched infusion in people with Chronic Graft vs Host Disease, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
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 10 inclusion and 14 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 23 May 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 Spain. 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?
Toxicity and maximum tolerated dose (time frame: Up 12 weeks after infusion). 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 NCT03683498, which also lists 1 linked publication.
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 23 May 2022.