NCT04070781

Itacitinib and Tocilizumab for Steroid Refractory Acute Graft Versus Host Disease

Phase I Study of Itacitinib in Combination With Tocilizumab for the Treatment of Steroid Refractory Acute Graft Versus Host Disease

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The study's primary objective is designed to assess the safety and tolerability, and determine the maximum tolerated dose (MTD) of both itacitinib and tocilizumab when given in combination to patients with steroid-refractory acute graft versus host disease (SR-aGVHD). The study's secondary objectives are to: * Estimate the day 28 response rate (ORR) \[complete response (CR), very good partial response (VGPR), and partial response (PR)\] of the combination of itacitinib and tocilizumab for the treatment of SR-aGVHD * Estimate the time to response and duration of response * Estimate the incidence of primary disease relapse while on study treatment * Estimate the incidence of infections including viral reactivation, bacterial infections and fungal infections while on study treatment * Estimate the progression-free survival (PFS), overall survival (OS), non-relapse mortality, GVHD-related mortality of study subjects * Estimate the proportion of patients who successfully discontinue steroids by 6 months and 12 months after therapy initiation

Detailed description

The treatment of acute and chronic GVHD consists mostly of steroids which has changed very little over the past 40 years. Response to current therapy for GVHD is far from perfect; only about 50% of patients respond to therapy and many of those responses are not durable. The current study is a phase I study dose de-escalation study where up to 6 patients will be enrolled into each dose level (2 levels), followed by an expansion cohort at the MTD. The goal of the study is to determine the maximum tolerated dose of the combination of itacitinib and tocilizumab. Once the MTD is determined, the investigator will enroll 10 additional patients as an expansion cohort to further define the safety profile of the combination and estimate its response rate.

Conditions

• Steroid Refractory GVHD
• Graft Vs Host Disease

Interventions

Type	Name	Description
DRUG	Itacitinib	Itacitinib is a novel, potent, and selective inhibitor of the Janus Kinase (JAK) family of protein tyrosine kinases (TYKs) with selectivity for Janus Kinase 1 (JAK1). Itacitinib is an investigational product. Itacitinib 200 mg daily in 28-day long cycles
DRUG	Tocilizumab	Tocilizumab is a biologic medication currently approved to treat adults with moderately to severely active rheumatoid arthritis (RA), adults with giant cell arteritis (GCA), and children ages two and above with Polyarticular Juvenile Idiopathic Arthritis (PJIA) or Systemic Juvenile Idiopathic Arthritis (SJIA). Tocilizumab blocks the inflammatory protein interleukin 6 (IL-6). This improves joint pain and swelling from arthritis and other symptoms caused by inflammation. Tocilizumab 4 or 8mg/kg cycle 1 day 1 every 4 weeks in 28-day cycles

Timeline

• Start date: 2020-01-20
• Primary completion: 2021-12-13
• Completion: 2021-12-13
• First posted: 2019-08-28
• Last updated: 2024-06-04

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study