NCT04097821

Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients

A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of combination treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, rineterkib and NIS793 in myelofibrosis (MF) subjects.

Detailed description

This open-label, multi-center, Phase Ib/II platform study design consisted of 3 parts. Part 1 was a Phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm a recommended Phase II dose. Dose escalation cohorts were treated with ruxoltinib + siremadlin or ruxolitinib + rineterkib. Safety run-in cohorts were treated with either ruxolitinb + sabatolimab, ruxolitinb + crizanlizumab or ruxolitinib + NIS7913. Parts 2 and 3 were Phase II selection and expansion, respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, an interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3. In June 2022, Novartis decided to permanently halt the study enrollment in all ongoing parts (Part 1 and Part 2), and Part 3 (expansion) was not initiated. With Protocol Amendment 8, an extension treatment phase of 12 cycles was added in Part 1 to allow access to the combination treatment for ongoing subjects deriving clinical benefit. In consideration of the enrollment halt, Parts 2 and 3 objectives were not pursued, and Part 1 objectives were updated accordingly.

Conditions

• Myelofibrosis

Interventions

Type	Name	Description
DRUG	Ruxolitinib	5 mg tablets for oral use
DRUG	Siremadlin	10 mg, 20 mg, or 40 mg capsules for oral use
DRUG	Crizanlizumab	100 mg/10 mL concentrate for infusion for intravenous use
DRUG	Sabatolimab	100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use
DRUG	Rineterkib	100 mg capsule for oral use
DRUG	NIS793	700 mg/7 mL concentrate for infusion for intravenous use

Timeline

• Start date: 2019-09-26
• Primary completion: 2023-05-03
• Completion: 2024-08-28
• First posted: 2019-09-20
• Last updated: 2025-08-07
• Results posted: 2025-08-07

Locations

22 sites across 13 countries: Australia, Canada, Denmark, Germany, Hungary, Italy, Netherlands, Russia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom