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

ClinicalTrials.gov Identifier: NCT04097821

Novartis Reference Number: CINC424H12201

Last Update: Dec 01, 2020

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The purpose of this study is to investigate the safety, pharmacokinetics and preliminary efficacy of combinations treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, LTT462 and NIS793 in myelofibrosis (MF) subjects.

Condition

Myelofibrosis

Phase

Phase 1

Phase 2

Overall status

Recruiting

Enrollment count

240 participants

Start date

Sep 26, 2019

Completion date

Jun 10, 2025

Gender

All

Age(s)

18 Years and older (Adult, Older Adult)

Interventions

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/mL concentrate for infusion for intravenous use

Drug

Sabatolimab

100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use

Drug

LTT462

100 mg capsule for oral use

Drug

NIS793

700 mg/7 mL concentrate for intravenous use

Eligibility Criteria

Inclusion Criteria:

Subjects have diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (ET) (PET-MF) or post-polycythemia vera (PV) myelofibrosis (PPV-MF) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria
Palpable spleen of at least 5 cm from the left costal margin (LCM) to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (a MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted).
Have been treated with ruxolitinib for at least 24 weeks prior to first dose of study treatment
Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day (BID)) for ≥ 8 weeks prior to first dose of study treatment

Exclusion Criteria:

Not able to understand and to comply with study instructions and requirements.
Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 half-lives of the study treatment, whichever is greater
Peripheral blood blasts count of > 10%.
Received a monoclonal antibody (Ab) or immunoglobulin-based agent within 1 year of screening, or has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic
Splenic irradiation within 6 months prior to the first dose of study drug
Received blood platelet transfusion within 28 days prior to first dose of study treatment.

Other protocol-defined Inclusion/Exclusion criteria may apply.