The objective of this clinical trial is to evaluate the efficacy (how well the drug works), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the study drug, RVU120, in treating adult patients with intermediate or high-risk, primary or secondary myelofibrosis. RVU120 will be given as a single agent or in combination with ruxolitinib.
The study schedule consists of a screening period up to 28 days, a 21-day treatment period, an end of treatment visit (30 days) and a 1-year follow-up where participants will be contacted every 3 months for assessment. Study duration for each participant will vary depending on the number of 21-day treatment cycles received. The study is open to participants aged ≥18 years with intermediate or high-risk, primary or secondary MF who have been previously treated, are ineligible for, or had a suboptimal response to JAK inhibitor therapy. Participants must have adequate organ function (kidney, liver) and no history of hematopoietic stem cell transplant. Participants may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Ruxolitinib is a kinase inhibitor which inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2
Policlinico Sant'Orsola-Malpighi
Bologna, Italy
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Brescia, Italy
To evaluate the number of participants with a response (anti-cancer activity) to RVU120 when administered as a single agent or in combination with ruxolitinib
The proportion of participants with spleen volume reduction (SVR) of ≥35% after 24 weeks of study treatment evaluated by magnetic resonance imaging (MRI) or computed tomography (CT)
Time frame: 12 months
To further evaluate the number of participants having a response (anti-cancer activity and/or clinical benefit) to RVU120 when administered as a single agent or in combination with ruxolitinib
The proportion of participants with ≥1 Grade bone marrow fibrosis improvement after 24 weeks of study treatment
Time frame: 12 months
Duration of spleen response
Assessed as the time from initial SVR of ≥35% by MRI/CT until disease progression or death, whichever occurs first
Time frame: 12 months
Number of participants with leukemic transformation
Assessed as the proportion of participants with bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting 2 weeks
Time frame: 12 months
Number of participants with hematological (clinical) improvement
Assessed as the proportion of participants with hematological (clinical) improvement as defined by International Working Group (IWG) Consensus Criteria (see Tefferi et al., 2006 for further details)
Time frame: 12 months
Progression-Free Survival (PFS)
Assessed as time from the time from first treatment to the first occurrence of disease progression or death
Time frame: 12 months
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Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
Catania, Italy
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l.
Meldola, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, Italy
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
Biała Podlaska, Poland
Szpital Uniwersytecki nr 2 im. dr Jana Biziela
Bydgoszcz, Poland
M2M Med. Sp. z o.o. Sp. j.
Chorzów, Poland
Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz
Gdansk, Poland
Pratia Hematologia Sp. z o.o.
Katowice, Poland
...and 8 more locations
Overall Survival (OS)
Assessed as time from the time from first treatment to death
Time frame: 12 months
Incidence and severity of adverse events (AEs)
Assessed as the number and grade of adverse events assessed by CTCAE v5.0
Time frame: 12 months
Change in symptom burden
Assessed as the proportion of participants achieving at least a 50% reduction in symptom burden after 24 weeks of commencing study treatment as assessed by the Total Symptom Score (TSS) using the Myelofibrosis Symptom Assessment Form (MFSAF). Each item is rated on a scale from 0 (Absent) to 10 (Worst Imaginable).
Time frame: Baseline and week 24
Absolute change in TSS from baseline
Assessed as the number of participants with absolute change in Total Symptom Score (TSS) from baseline assessed using the Myelofibrosis Symptom Assessment Form (MFSAF). Each item is rated on a scale from 0 (Absent) to 10 (Worst Imaginable).
Time frame: Baseline and week 24