Donor Regulatory T Cells Infusion in Patients With Chronic Graft-versus-host Disease (GVHD)

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The immune system has offensive and defensive capacities. In bone marrow transplantation, offensive cells in the donor grafts may attack host's organs, leading to a complication known as Graft versus Host Disease (GVDH). At present, patients receive steroid treatment to combat this tricky situation. Nevertheless, some patients do not respond to this therapy. Recently, it has been shown that immune system cells having defensive capacities can help in preventing the occurrence of a GVDH.

This study aims to evaluate if these protective cells together with a non-standard immunosuppressor can improve the clinical condition and suppress the activity of the offensive cells in the graft.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital of Liege; University of Liege
• Treatments: Everolimus; Sirolimus

Criteria

1. Patient criteria : Donor Treg infusion (DTI) and control arms.

• Signed informed consent.

• Grafts from HLA-identical siblings or HLA-matched unrelated donor (1 of 10 HLA-mismatch is allowed).

• ≥ 18 years of age.

• Steroid-refractory or steroid-resistant chronic GVHD defined as:

• development of 1 or more new sites of disease while being treated for chronic GVHD,

• progression of existing sites of disease while receiving treatment for chronic GVHD,

• failure to improve despite at least 1 month of standard treatment for chronic GVHD.

or severe chronic GVHD and contra-indication to the use of steroids and at least failed one prior line of treatment.

• Severe chronic GVHD according to NIH definition.

• No prior failure of rapamycine as treatment for chronic GVHD

• No contra-indication to the use of rapamycin.

• No alemtuzumab administration in the last 6 months.

• GFR > 25 mL/min.

• No HIV seropositivity.

• No fungal infection with radiological progression after treatment with amphotericine B or active azoles for > 1 month.

• No other uncontrolled infection.

• No progression of the hematological malignancy.

• Karnofsky performance score ≥ 70%.

• DLCO > 35% and no need of supplemental continuous oxygen.

• No active post-transplant microangiopathy and no previous microangiopathy while on rapamycine.

• No uncontrolled hypertriglyceridemia.

2 Donor criteria : DTI arm only.

• Donor ≥ 18 years of age.

• Written informed consent to perform apheresis from the donor (all patients) and permission from the third party donor registry (in case of unrelated donor).

• Standard criteria for leukapheresis and DLI following complete work-up according to standard procedures.