Treatment of steroid-resistant chronic graft-versus-host-disease with regulatory T cells

Phase 1

• Conditions: Treatment of steroid-resistant chronic graft-versus-host disease with donor-derived regulatory T cells; MedDRA version: 20.0 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-003947-12-DE
• Lead Sponsor: Freistaat Bayern represented by University of Regensburg represented by Kaufmännischer Direktor

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-02-02
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 27

Inclusion Criteria

The following criteria on screening examination have to be fulfilled:
•Steroid-refractory moderate to severe cGVHD despite use of two or more agents (failure of 2nd line treatment). Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) 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 other glucocorticoids) without complete resolution of signs and symptoms and continuing moderate to severe cGVHD.
•Steroid-dependent cGVHD as indicated if >0.25 mg/kg/d prednisone are needed to prevent cGVHD recurrence or progression on 2nd line treatment or subsequent treatment lines as illustrated by two failed attempts to taper with a more than 8 wks interval
•No dose-escalation of glucocorticoids beyond the maximum dose of the prior cGVHD treatment line within 4 wks of enrolment
•No addition of other immunosuppressive medications (e.g., calci-neurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of the drug
•ECOG performance status 0-2 (Appendix X, section X)
•Participants must have adequate organ function as defined below:
Hepatic: Adequate hepatic function (total bilirubin <2.0 mg/dl-exception permitted in participants with Gilbert’s Syndrome; AST (SGOT)/ALT (SGPT) =2x ULN), unless hepatic dysfunction is a manifestation of proven or presumed cGVHD. Abnormal LFTs in the context of active cGVHD involving other organ systems is permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD.
Pulmonary: FEV1 = 50% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD.
•Age 18 -75 y
•Written informed consent of patient

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

•Age <18 y and >75 y
•No previous steroid therapy
•Severe psychiatric disorders
•Presumed life expectancy < 4 wks
•Lack of informed consent from patient
•Donors from outside EU (NMDP, Canadian donor registrar)
•Participation in another interventional clinical trial according to the AMG (Arzneimittel¬gesetz) within 30 days prior to inclusion
• T cell-depleting antibody therapy within the last 30d before enrolment
•Pregnant or nursing woman. Sexually active women with childbearing potential or sexually active male patients unwilling to use an effective form of contraception during participation in the study from time of inclusion until 2 months after Treg therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To examine the safety and MTD Level of in vitro expanded donor regulatory T cells for the Treatment of patients with chronic GVHD;<br> Secondary Objective: To assess the clinical response to Treg treatment <br> To assess immunologic effects of Treg treatment<br> To determine predictors of clinical Response<br> ;Primary end point(s): Toxicity and MTD of Treg-infusion at 4 weeks;Timepoint(s) of evaluation of this end point: 1month after therapy

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): Feasibility of donor Treg infusion<br> Clinical response of Treg-treated patients at 12 & 24wks after Treg infusion<br> Immunologic effects of Treg treatment within 12 weeks<br> ;Timepoint(s) of evaluation of this end point: wk 1, 4, 8, 12, 24