Infusion of donor T-cells for patients with chronic graft versus host disease

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

This study is testing whether infusing special donor T-cells can help patients with chronic graft versus host disease who haven't improved with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sex: All
• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Academic / other)
• Drugs / interventions: rituximab, ruxolitinib, prednisone
• Locations: 1 site (Sevilla)
• Trial ID: NCT05095649 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the effectiveness of donor regulatory T-cell enriched infusions in patients suffering from steroid-refractory chronic graft versus host disease (cGVHD) who have not achieved complete remission after 12 weeks of treatment with ruxolitinib. A total of 15 patients will be enrolled, and the study will assess survival rates one year post-infusion using Kaplan Meier curves. The Treg-enriched cells will be administered at a dose of 2x10^6 cells/kg. The trial aims to provide a new therapeutic option for patients who have not responded adequately to existing treatments.

Who should consider this trial

Good fit: Ideal candidates include patients who have undergone allogeneic hematopoietic stem cell transplantation and have steroid-refractory cGVHD.

Not a fit: Patients who have not received prior treatment with ruxolitinib or those with progressive disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for patients with chronic graft versus host disease who have not responded to standard therapies.

How similar studies have performed: While there is ongoing research in the area of T-cell therapies for cGVHD, this specific approach using donor regulatory T-cells in steroid-refractory cases is relatively novel.

Eligibility criteria

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.

Where this trial is running

Sevilla

• José Antonio Pérez Simón — Sevilla, Spain (Recruiting)

Study contacts

• Principal investigator: José Antonio Pérez-Simón, M.D. Ph.D — Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.
• Study coordinator: José Antonio Pérez-Simón, M.D. Ph.D

Conditions Chronic Graft vs Host Disease; Ruxolitinib; T cells