About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years
Diagnosis of Primary or Secondary myelofibrosis (MF) according to the revised World Health Organization (WHO) criteria (Arber 2022).
Intermediate or high-risk disease.
Resistant or refractory to prior Janus kinase (JAK) inhibitor treatment or ineligible for JAK inhibitor treatment in the opinion of the investigator; or Suboptimal response to JAK inhibitor treatment. Note: a suboptimal response to JAK inhibitor treatment is defined as spleen size increase by palpation >25% after the first 3 months of treatment with a JAK inhibitor or persistent splenomegaly (spleen volume of >450 cm3) after at least 6 months of JAK inhibitor treatment and presence of 1 symptom score ≥5 or 2 symptom scores ≥3, new or persistent red blood cell (RBC) transfusion dependence; or may include participants naïve to previous treatment with JAK inhibitor.
Disqualifiers
Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
Prior history of hematopoietic stem cell transplant.
Participation in any other study in which receipt of an investigational new drug occurred within 4 weeks prior to Cycle 1 Day 1.
Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
Trial design
Parallel
Treatments tested in this trial
RVU120
DrugRVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Ruxolitinib
DrugRuxolitinib is a kinase inhibitor which inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2
Treatment groups
Trial outcomes
Primary outcomes
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)
Secondary outcomes
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
Duration of spleen response
Assessed as the time from initial SVR of ≥35% by MRI/CT until disease progression or death, whichever occurs first
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
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)
Sponsors and contacts
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