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: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Criteria

Inclusion Criteria:

• Age (>18 years)

• Any type of peripheral blood stem cell transplant (matched-related, match non-related, and haplo)

• Any conditioning regimen

• Newly diagnosed moderate to severe chronic graft versus host disease

• Steroid refractory moderate to severe chronic graft versus host disease defined as progression with prednisone 1mg/kg/day, or stable disease after four to six weeks of prednisone >0.5 mg/kg/day, or disease progression when reducing prednisone below <0.5 mg/kg/día.

5. Eastern Cooperative Oncology Group (ECOG) <= 2

Exclusion Criteria:

• Disease relapse (excluding positive minimal residual disease)

• Secondary malignancies

• Disease progression

• Use of B lymphocyte cytotoxics in the last month (i.e., rituximab, bortezomib)

• Advance stages of heart failure (NYHA III o IV)

• Ventricular arrhythmias

• Uncontrolled hypertension

• Ischemic heart diseases such as unstable angina or stable angina in the last six months

• Hepatitis B or C

• Hypersensitivity to ibrutinib

• Active bleeding

• Uncontrolled acute infection

• Hepatopathy Child-Pugh C

• Pregnancy