Chronic Graft vs Host DiseasePhase 2Treg4GVHDNCT05095649
Donor Regulatory T-cells for cGVHD in Patients Who do Not Obtain Complete Remission With Ruxolitinib
A Phase 2 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
Phase II clinical trial to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission under treatment with ruxolitinib Read more about this study
- Who is it for?
- Any age
- 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
- 15 participants
- Where
- 1 siteSpain
- Study dates
- 24 Mar 2022to 15 Feb 2026
- Phase
- Phase 2
- 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
- No healthy volunteers
- 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 any response other than progression after at least 12 weeks of treatment with ruxolitinib. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD 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 enrollment.
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. 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.
- Eastern Cooperative Oncology Group scale performance status 0-2
Show all 9Show fewer
- 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 active thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura in the last 6 months.
- New immunosuppressive medication in the 4 weeks prior to enrollment.
- Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior to enrollment.
- Post-transplant exposure to T-cell or interleukin-2 targeted medication within 100 days prior to enrollment.
Show all 14Show fewer
- Donor lymphocyte infusion within 100 days prior to enrollment.
- Active malignant relapse.
- Active uncontrolled infection.
- Organ transplant (allograft) recipient.
- HIV-positive individuals on combination antiretroviral therapy are ineligible.
- 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.
- Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator.
- Pregnant women are excluded from this study.
Trial locations and contacts
1 site in 1 country.
José Antonio Pérez-Simón, M.D. Ph.D contact
Spain1 site, 1 recruiting
- Recruiting
José Antonio Pérez Simón
Seville, 41011
José Antonio Pérez Simón, PhD, josea.perez.simon.sspa@juntadeandalucia.es
About this study
Official title: Phase II Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in Patients Who do Not Obtain Complete Remission With Ruxolitinib
Phase II clinical trial to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission under treatment with ruxolitinib
Read the detailed description
A number of 15 patients will be included to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission after 12 weeks of treatment with ruxolitinib.
The doses of Treg-enriched cells will be 2x10^6 cells/kg.
Survival at 1 year after Treg infusion will be represented based on the clinical data with Kaplan Meier curves.
- 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 cluster of differentiation 25hi regulatory T cells from cluster of differentiation antigen 8 and/or cluster of differentiation antigen19 pre-depleted leukapheresis products.
| Study group | Role | What they receive |
|---|---|---|
| Regulatory T-cell enriched infusion | Experimental | The doses of Regulatory T-cell enriched infusion will be 2x10^6 cells/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.
Number of Participants with overall response rate.
Obtain ≥65% the overall response rate at 6 months after infusion
Measured: 6 months post-infusion
Number of Participants with overall response rate.
Obtain ≥75% the overall response rate at 1 year after infusion
Measured: 1 year post-infusion
Survival
Number of patients who survive after Regulatory T-cell enriched infusion
Measured: 1 year after Regulatory T-cell enriched infusion
Secondary outcomes (14)
Disease evaluation through Symptoms of the disease
Symptoms of the disease through chronic graft-versus-host disease activity assessment (clinician) according to NIH consensus- form A
Measured: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Disease evaluation through measurement of quality of life
Measurement of quality of life through Functional Assessment of Cancer Therapy - Bone Marrow Transplantation
Measured: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Disease evaluation through Symptoms of the disease
Symptoms of the disease through chronic graft-versus-host disease symptom scoring scale
Measured: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Immunosuppressive requirements.
Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication
Measured: Screening, month1, months 3, 6, and 12 after infusion
Free survival
To evaluate failure free survival (change of immunosuppression, mortality or relapse)
Measured: 1 year after infusion.
Immunologic monitoring and in vivo Treg tracking through immune globulins
Quantitative immune globulins
Measured: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through plasma
Plasma banking
Measured: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through mononuclear cells
Storage of additional mononuclear cells
Measured: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through lymphocyte
Detailed immunological evaluation of lymphocyte
Measured: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets
Quantitative Natural Killer cell subsets
Measured: 1 year after infusion and after infusion
Purity of Treg-enriched cell infusion
Percentage of cells viability, negative gram stain/endotoxin, percentage of cluster of differentiation 4+ cluster of differentiation 25+ cells and cluster of differentiation 4+cluster of differentiation25+cluster of differentiation127- Treg in order to consider for the infusion.
Measured: Before 24 hours to infusion up infusion day
Toxicity monitoring of Treg-enriched cells
Number of grade 3 or higher Adverse Events and all Serious Adverse Events according to the Version 5.0 of the NCI Common Terminology Criteria for Adverse Events.
Measured: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Life-threatening infections
Number of infections
Measured: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Predictors of clinical response
Quantify predictors of clinical response among patients receiving ruxolitinib
Measured: 1 year after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2021
- Study start24 Mar 2022
- Primary completion15 Aug 2025 (estimated)
- Study completion15 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The doses of Treg-enriched cells will be 2x10\^6 cells/kg
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
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
- NCT05095649
- Sponsor's protocol ID
- Treg4GVHD
- Acronym
- Treg4GVHD
- Status last verified
- Mar 2024
- First submitted
- 26 May 2021
- Last updated
- 26 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II 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
- NCT05095649
- Acronym / sponsor ID
- Treg4GVHD / Treg4GVHD
- Conditions
- Chronic Graft vs Host Disease
- Keywords
- Ruxolitinib, T cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 24 Mar 2022 (actual)
- Primary completion
- 15 Aug 2025 (estimated)
- Study completion
- 15 Feb 2026 (estimated)
- First posted
- 27 Oct 2021 (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.
Phase II clinical trial to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission under treatment with ruxolitinib
Detailed description
A number of 15 patients will be included to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission after 12 weeks of treatment with ruxolitinib.
The doses of Treg-enriched cells will be 2x10^6 cells/kg.
Survival at 1 year after Treg infusion will be represented based on the clinical data with Kaplan Meier curves.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The doses of Treg-enriched cells will be 2x10^6 cells/kg
| Arm | Type | Receives |
|---|---|---|
| Regulatory T-cell enriched infusion | Experimental | Biological: Regulatory T-cell enriched infusionThe doses of Regulatory T-cell enriched infusion will be 2x10^6 cells/kg |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Recipient of allogeneic hematopoietic stem cell transplantation
- Participants must have steroid-refractory cGVHD and had obtained any response other than progression after at least 12 weeks of treatment with ruxolitinib. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD 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 enrollment.
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. 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.
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 active thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura in the last 6 months.
- New immunosuppressive medication in the 4 weeks prior to enrollment.
- Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior to enrollment.
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 cluster of differentiation 25hi regulatory T cells from cluster of differentiation antigen 8 and/or cluster of differentiation antigen19 pre-depleted leukapheresis products. | Biological | Regulatory T-cell enriched infusion |
Primary outcome
Number of Participants with overall response rate.
Time frame: 6 months post-infusion
Obtain ≥65% the overall response rate at 6 months after infusion
Number of Participants with overall response rate.
Time frame: 1 year post-infusion
Obtain ≥75% the overall response rate at 1 year after infusion
Survival
Time frame: 1 year after Regulatory T-cell enriched infusion
Number of patients who survive after Regulatory T-cell enriched infusion
14 secondary outcomes
Disease evaluation through Symptoms of the disease
Time frame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Disease evaluation through measurement of quality of life
Time frame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Disease evaluation through Symptoms of the disease
Time frame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Immunosuppressive requirements.
Time frame: Screening, month1, months 3, 6, and 12 after infusion
Free survival
Time frame: 1 year after infusion.
Immunologic monitoring and in vivo Treg tracking through immune globulins
Time frame: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through plasma
Time frame: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through mononuclear cells
Time frame: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through lymphocyte
Time frame: 1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets
Time frame: 1 year after infusion and after infusion
Purity of Treg-enriched cell infusion
Time frame: Before 24 hours to infusion up infusion day
Toxicity monitoring of Treg-enriched cells
Time frame: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Life-threatening infections
Time frame: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Predictors of clinical response
Time frame: 1 year after infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
- Individual participant dataSharing planned: No
Related trials for Chronic Graft vs Host Disease
RecruitingPhase 1/2
Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Graft vs Host Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
Recruiting
Effect of Anomia Rehabilitation Combined With Metacognitive Training in Patients With Chronic Vascular Aphasia
Aphasia, Stroke
Not yet recruiting
A New ECP Protocol for the Treatment of cGVHD
Chronic Graft Versus Host Disease
Active, not recruitingPhase 1/2
Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor, in Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Chronic Graft vs Host Disease, Chronic Graft-Versus-Host Disease
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 contact
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 2 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 9 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: status not confirmed, as of the sponsor's last update on 26 Mar 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact José Antonio Pérez-Simón, M.D. Ph.D (955013414 ext. 0034, josea.perez.simon.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with overall response rate. (time frame: 6 months post-infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Mar 2024.