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

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: Recruiting
• Conditions: Chronic Graft vs Host Disease
• Intervention / Treatment: Biological: Regulatory T-cell enriched infusion

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: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: José Antonio Pérez-Simón, M.D. Ph.D; Phone Number: 0034 955013414; Email: josea.perez.simon.sspa@juntadeandalucia.es
• Study Contact Backup: Name: Clara M. Rosso, M.D. Ph.D; Phone Number: 0034 955013414; Email: claram.rosso.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Sevilla, Spain, 41011
    • Recruiting
    • José Antonio Pérez Simón
    • Contact: José Antonio Pérez Simón, PhD; Email: josea.perez.simon.sspa@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Number of Participants with overall response rate.	Obtain ≥65% the overall response rate at 6 months after infusion	6 months post-infusion
Number of Participants with overall response rate.	Obtain ≥75% the overall response rate at 1 year after infusion	1 year post-infusion
Survival	Number of patients who survive after Regulatory T-cell enriched infusion	1 year after Regulatory T-cell enriched infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease evaluation through measurement of quality of life	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.	Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication	Screening, month1, months 3, 6, and 12 after infusion
Free survival	To evaluate failure free survival (change of immunosuppression, mortality or relapse)	1 year after infusion.
Immunologic monitoring and in vivo Treg tracking through plasma	Plasma banking	1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through mononuclear cells	Storage of additional mononuclear cells	1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through lymphocyte	Detailed immunological evaluation of lymphocyte	1 year after infusion and after infusion
Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets	Quantitative Natural Killer cell subsets	1 year after infusion and after infusion
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.	Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
Life-threatening infections	Number of infections	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	1 year after infusion
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	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	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	Quantitative immune globulins	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.	Before 24 hours to infusion up infusion day

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: José Antonio Pérez-Simón, M.D. Ph.D, Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Estimated): August 15, 2025
• Study Completion (Estimated): February 15, 2026

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ruxolitinib; T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID 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