Efficacy and Safety of Low-dose Ibrutinib and Itraconazole in Chronic Graft Versus Host Disease
Status:
Recruiting
Trial end date:
2023-08-01
Target enrollment:
Participant gender:
Summary
Chronic graft-versus-host disease (cGVHD) affects 30 to 70% of Allogeneic Hematopoietic Cell
Transplantation, decreases the quality of life, and increases mortality. First-line
treatments for cGVHD are steroids, however, up to 50% of patients do not respond to
treatment. There is no well-defined second-line treatment for cGVHD, but ibrutinib, a Bruton
tyrosine kinase inhibitor, has been successfully used in phase 2 clinical trials for moderate
to severe steroid-refractory cGVHD and has been shown to be safe, showing rates of response
of 69% at a median follow-up of 26 months. Therefore, ibrutinib was approved by the FDA for
the treatment of steroid-refractory cGVHD. Also, it is known that ibrutinib is metabolized by
cytochrome isoenzyme 3A4 and that itraconazole is a potent inhibitor of this hepatic
isoenzyme. Therefore, the investigators hypothesized that in subjects with newly diagnosed
cGVHD and in patients with steroid-refractory cGVHD, low-dose ibrutinib in combination with
itraconazole might be effective and safe.