A randomized, open-label, phase I/II open platform study evaluating safety and efficacy of novel ruxolitinib combinations in myelofibrosis patients
- Conditions
- myelofibrosis10018849
- Registration Number
- NL-OMON52828
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 7
* 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 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
* Part 1: Platelet counts * 75 000/*L
* Part 2 and Part 3: Platelet counts * 50 000/*L
* 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. PRBC transfusions are permitted
* Subjects with known TP53 mutation or deletion of TP53
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The efficacy assessments for the primary objectives are:<br /><br>**Laboratory hemoglobin assessments taken at the end of Cycle 6 compared to<br /><br>baseline<br /><br>**MRI or CT imaging of the spleen will be performed at screening, at the end of<br /><br>Cycle 6, the end of Cycle 12 and at end of treatment (EOT)<br /><br>**total symptom score (TSS) assessed by MFSAF v4.0 at baseline and at the end<br /><br>of Cycle 6</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess the proportion of subjects in each treatment arm who achieve an Hb<br /><br>improvement of * 2.0 g/dL or * 1.5 g/dL from baseline to the end of<br /><br>Cycle 6 and end of Cycle 12<br /><br>To evaluate the changes in spleen size in each treatment arm measured by change<br /><br>in spleen length (by palpation) and spleen volume (by<br /><br>magnetic resonance imaging (MRI)/computed topography (CT)) from baseline<br /><br>To evaluate changes in symptoms of myelofibrosis in each treatment arm using<br /><br>MFSAF v4.0 and European Organization for Research and<br /><br>Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)<br /><br>patient reported outcomes (PROs) from baseline<br /><br>To characterize the pharmacokinetic profile of ruxolitinib administered in<br /><br>combination with siremadlin, crizanlizumab, sabatolimab, LTT462 and NIS793. </p><br>