Donor Regulatory T-cells for cGVHD in Patients Who do Not Obtain Complete Remission With Ruxolitinib (Treg4GVHD)

March 25, 2024 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Regulatory T-cell enriched infusion
The doses of Regulatory T-cell enriched infusion will be 2x10^6 cells/kg
Biological: Regulatory T-cell enriched infusion
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants with overall response rate.
Time Frame: 6 months post-infusion
Obtain ≥65% the overall response rate at 6 months after infusion
6 months post-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
1 year post-infusion
Survival
Time Frame: 1 year after Regulatory T-cell enriched infusion
Number of patients who survive after Regulatory T-cell enriched infusion
1 year after Regulatory T-cell enriched infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Measurement of quality of life through Functional Assessment of Cancer Therapy - Bone Marrow Transplantation
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
Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication
Screening, month1, months 3, 6, and 12 after infusion
Free survival
Time Frame: 1 year after infusion.
To evaluate failure free survival (change of immunosuppression, mortality or relapse)
1 year after infusion.
Immunologic monitoring and in vivo Treg tracking through plasma
Time Frame: 1 year after infusion and after infusion
Plasma banking
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
Storage of additional mononuclear cells
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
Detailed immunological evaluation of lymphocyte
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
Quantitative Natural Killer cell subsets
1 year after infusion and after infusion
Toxicity monitoring of Treg-enriched cells
Time Frame: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
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.
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
Number of infections
Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Predictors of clinical response
Time Frame: 1 year after infusion
Quantify predictors of clinical response among patients receiving ruxolitinib
1 year 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
Symptoms of the disease through chronic graft-versus-host disease activity assessment (clinician) according to NIH consensus- form A
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
Symptoms of the disease through chronic graft-versus-host disease symptom scoring scale
Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
Immunologic monitoring and in vivo Treg tracking through immune globulins
Time Frame: 1 year after infusion and after infusion
Quantitative immune globulins
1 year after infusion and after infusion
Purity of Treg-enriched cell infusion
Time Frame: Before 24 hours to infusion up infusion day
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.
Before 24 hours to infusion up infusion day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: José Antonio Pérez-Simón, M.D. Ph.D, Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 27, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Treg4GVHD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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