A safety, pharmacokinetics and preliminary efficacy study of novel ruxolitinib combination treatments in patients with myelofibrosis

Phase 1

• Conditions: PMF or PPV- MF, or PET- MF; MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000373-23-NL
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-22
• Last Update Posted: 30 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 240

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 12 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 = 4 weeks prior to first dose of study treatment.
• Hemoglobin < 11 g/dL (= 6.8 mmol/L)
• Part 1: Platelet counts = 75 000/µL
• Part 2 and Part 3: Platelet counts = 50 000/µL

Additional inclusion criteria as per full protocol may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 177
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63

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%.
•Had history of documented severe hypersensitivity
reactions/immunogenicity to a prior biologic product in any treatment arm OR received a monoclonal antibody (Ab) or immunoglobulin-based agent
-for treatment arms with NIS793, crizanlizumab or sabatolimab within 1 year of screening
-for treatment arms with rineterkib or siremadlin arms within <=4 weeks of screening or <=5 half-lives whichever is shorter for rineterkib or siremadlin arms
-for Part 2 and Part 3, the longest window will apply based on the compounds opened for randomization
•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. NOTE: PRBC transfusions are permitted
•Subjects with known TP53 mutation or deletion of TP53
Additional exclusion criteria as per full protocol may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified