A Phase 1b/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 592 in Adult Subjects With Steroid Refractory Chronic Graft Versus Host Disease (cGVHD)
- The phase 1b portion : multiple ascending dose study. Each dosing cohort will consist of 3 subjects who will receive either weekly or biweekly AMG 592 plus protocol permitted background therapy for up to 52 weeks.
- The phase 2 portion : single arm, multi-center, open‑label trial in subjects with steroid refractory cGVHD. All subjects will receive the recommended phase 2 dose of AMG 592 for up to 52 weeks plus protocol permitted background therapy for cGVHD.
- 18 years of older
- Recipient of an allogeneic hematopoietic stem cell transplantation
- Moderate to severe steroid-refractory cGVHD
- No more than 3 previous treatments for cGVHD, excluding topical agents
- Stable dose of ≤ 1 mg/kg/day of systemic prednisone or equivalent for at least 2 weeks prior to first dose of AMG 592
- Stable dose of non-corticosteroid immunosuppressants for the 2 weeks prior to first dose of AMG 592
- Karnofsky performance status score ≥ 50%
- Concurrently receiving treatment with calcineurin-inhibitor plus sirolimus
- Received ibrutinib or following therapies considered investigational for treatment of cGVHD including imatinib, bortezomib, ruxolitnib, or entospletinib, within 4 wks prior to starting AMG 592 or is currently receiving treatment in another investigational drug or device study
- Donor lymphocyte infusion within 12 wks prior to starting dose of AMG 592
- University Hospital Leuven Gasthuisberg