Glasdegib in Refractory Patients With Sclerotic Chronic Graft-Versus-Host Disease

Summary

This is a phase 1b/2a, open label, multi-centre, safety and efficacy study of glasdegib in patients with sclerotic cGVHD refractory to second-line treatment. The design for the current study is a standard 3+3 dose-finding scheme. A dose escalation/de-escalation design will be applied in successive patient cohorts until identification of MTD. Glasdegib will be self-administered orally once daily in the morning as monotherapy in continuous 28-day treatment cycles for a maximum of 24 cycles. Those patients enrolled in the trial that obtain objective clinical benefit under treatment with glasdegib (defined as the achievement of at least a partial response at one or more target organs), will be allowed to proceed to a slow dose withdrawal phase over a period of 6 months after the end of Cycle 24.

Timeline

Start

2018-01-09

Primary completion

2022-01-09

Completion

2022-06-09

Publications

• Background Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, Lee SJ, Carpenter PA, Sandmaier BM, Hansen JA, Martin PJ, Flowers ME. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood. 2013 Jun 20;121(25):5098-103. doi: 10.1182/blood-2012-10-464198. Epub 2013 Apr 1.
• Background Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):46-61. doi: 10.1111/j.1365-2141.2012.09128.x. Epub 2012 Apr 26.
• Background Zerr P, Palumbo-Zerr K, Distler A, Tomcik M, Vollath S, Munoz LE, Beyer C, Dees C, Egberts F, Tinazzi I, Del Galdo F, Distler O, Schett G, Spriewald BM, Distler JH. Inhibition of hedgehog signaling for the treatment of murine sclerodermatous chronic graft-versus-host disease. Blood. 2012 Oct 4;120(14):2909-17. doi: 10.1182/blood-2012-01-403428. Epub 2012 Aug 22.

Drugs

Indications