NCT05348096

Efficacy and Safety of Low-dose Ibrutinib and Itraconazole in Chronic Graft Versus Host Disease

Efficacy and Safety of the Combination of Low-dose Ibrutinib and Itraconazole in Moderate to Severe Chronic Graft Versus Host Disease: a Phase 2 Trial

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (estimated)
• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In this phase 2 clinical trial, patients with newly diagnosed cGVHD and refractory cGVHD will receive low-dose ibrutinib (140mg/day) combined with a cytochrome 3A4 inhibitor (itraconazole, 100mg BID) for six months. The follow-up consists of weekly visits for the first months and then monthly for six months. The investigators will address clinical and biochemical parameters in each visit and grade severity using the NIH (2014) scale. Also, patients will answer the modified Lee symptom scale, and grade response to treatment using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). The investigators will grade adverse events with the Common Terminology Criteria for Adverse Events \[v5.0\]. The investigators will report proportion and time to any response, complete response, partial response, stable disease, and progression. Also, the investigators will report the proportion of patients that interrupted steroids for at least one month, the proportion of patients that interrupted every immunosuppressive therapy for at least one month, and the proportion of patients that interrupted ibrutinib specifying the cause of the interruption.

Conditions

• Chronic Graft-versus-host-disease

Interventions

Type	Name	Description
DRUG	Low-dose ibrutinib	Daily ibrutinib (140mg QD) and itraconazole (100mg BID) for six months.

Timeline

• Start date: 2022-04-01
• Primary completion: 2023-04-01
• Completion: 2023-08-01
• First posted: 2022-04-27
• Last updated: 2022-04-27

Locations

1 site across 1 country: Mexico