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-DE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-08-14
• Last Update Posted: 21 May 2024

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

Key inclusion criteria for the extension treatment phase are listed below,
please refer to the protocol for the full list of inclusion criteria:
• Signed informed consent form prior to participation
• On going in the core treatment phase
• Demonstrated clinical benefit in the core treatment phase per
investigator's assessment.

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
• Use of systemic steroid therapy and other immunosuppressive drugs
within 14 days prior to first dose of study treatment (> 10 mg/day
prednisone or equivalent). Topical, inhaled, nasal, and ophthalmic
steroids are allowed. Replacement therapy, steroids given in the context
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of a transfusion are allowed and not considered a form of systemic
treatment.
• Occurrence of any clinically significant bleeding events within 6
months prior to first dose of study treatment.
• For patients treated with rineterkib in Part 1 and for all patients in
Part 2 and Part 3 (if an rineterkib arm is included in the randomization
for Part 2 or Part 3): Pre-existing retinal vein occlusion (RVO) or current
risk factors (apart from the underlying MF) for RVO.
Key exclusion criteria for the extension treatment phase are listed
below, please refer to the protocol for the full list of exclusion criteria:
• Patient meeting the list of discontinuation criteria
• Evidence of treatment failure
• Enrollment in another interventional study
• Non-compliance of the subject or consent withdrawal
• Unresolved toxicities for which treatment has been interrupted in the
core treatment phase
• Subject has local access to alternative myelofibrosis treatment as
assessed suitable in the opinion of the investigator.

Study & Design

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