RVU120 in Patients With Intermediate or High-risk, Primary or Secondary Myelofibrosis

NCT06397313 | Recruiting Phase 2 DMC

• 1 other identifier: POTAMI-61
• Study Type: interventional
• Target: 230
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

Myelofibrosis

Keywords

intermediate; high-risk; primary; secondary

Outcome Measures

Primary Outcomes (1)

• 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)

  12 months

Secondary Outcomes (9)

• 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

  12 months

• Duration of spleen response

  12 months

• Number of participants with leukemic transformation

  12 months

• Number of participants with hematological (clinical) improvement

  12 months

• Progression-Free Survival (PFS)

  12 months

Study Arms (2)

RVU120

EXPERIMENTAL

Cohort 1 RVU120 is administered at 250 mg as a single agent every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles, or at an adjusted dose, to participants with intermediate or high-risk, primary or secondary MF who have been previously treated with or are ineligible for treatment with a JAK inhibitor.

Drug: RVU120

RVU120 + ruxolitinib

EXPERIMENTAL

Cohort 2 RVU120 is administered at 250 mg every other day on days 1, 3, 5, 7, 9, 11, and 13 of 21-day treatment cycles or at an adjusted dose, in combined with ruxolitinib administered orally twice daily following the dosing instructions in current prescribing information, to participants with intermediate or high risk, primary or secondary MF experiencing suboptimal response to JAK inhibitor.

Drug: RVU120; Drug: Ruxolitinib

Interventions

RVU120 DRUG

RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19

Also known as: SEL120

RVU120; RVU120 + ruxolitinib

Ruxolitinib DRUG

Ruxolitinib is a kinase inhibitor which inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2

Also known as: RUX

RVU120 + ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable splenomegaly as demonstrated by palpable spleen measuring ≥5 cm below the left costal margin. The edge of the spleen should be measured from the mid-clavicular line on the left side of the abdomen to the point of greatest splenic protrusion; or spleen volume of ≥450 cm3 measured by magnetic resonance imaging(MRI) or computed tomography (CT).
• Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the following symptoms: night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, bone or muscle pain, and inactivity.
• Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
• Adequate hematologic function defined as:
• absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support)
• platelet count ≥50 × 109/L (Cohort 2 and Cohort 3 only)
• Adequate renal function defined as calculated or measured creatinine clearance (CrCl) of ≥30 mL/minute using the formula of Cockcroft and Gault (see Section 15).
• Adequate liver function defined as (a) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN); (b) alkaline phosphatase (ALP) ≤2 × ULN (ALP ≤5 × ULN for participants with isozymes specific to bone); (c) bilirubin \<2 × ULN or bilirubin ≤3 × ULN if due to Gilbert's disease.

You may not qualify if:

• Each participant must not meet any of the following:
• 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.
• Active known second malignancy with the exception of any of the following:
• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
• Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
• Low-risk prostate cancer with a Gleason score \<7 and a prostate-specific antigen (PSA) level \<10 ng/mL
• Any other cancer from which the participant has been disease-free for ≥3 years.
• Known or suspected allergy to RVU120 or RUX.
• Impairment of gastrointestinal function or gastrointestinal disease
• Major surgical procedure or significant traumatic injury within 28 days Placement of a vascular access device or minor surgery is permitted within 14 days before Cycle 1 Day 1 (provided that the wound has healed).
• Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
• Significant cardiac dysfunction defined as myocardial infarction within 12 months of Cycle 1 Day 1, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina (Section 17), or left ventricular ejection fraction (LVEF) \<40% as per echocardiography or multiple gated acquisition (MUGA) scan.
• Taking any medications, herbal supplements, or other substances (including smoking) that are known to be strong inhibitors or moderate/strong inducers or sensitive substrates of CYP1A2, within less than 5 half-lives prior to Cycle 1 Day 1.

Sponsors & Collaborators

• Ryvu Therapeutics SA: lead

Study Sites (18)

Policlinico Sant'Orsola-Malpighi

Bologna, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"

Catania, Italy

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l.

Meldola, Italy

RECRUITING

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Italy

RECRUITING

Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej

Biała Podlaska, Poland

RECRUITING

Szpital Uniwersytecki nr 2 im. dr Jana Biziela

Bydgoszcz, Poland

RECRUITING

M2M Med. Sp. z o.o. Sp. j.

Chorzów, Poland

RECRUITING

Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz

Gdansk, Poland

RECRUITING

Pratia Hematologia Sp. z o.o.

Katowice, Poland

RECRUITING

Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej

Kielce, Poland

COMPLETED

Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

Krakow, Poland

RECRUITING

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie

Lublin, Poland

RECRUITING

Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, Poland

RECRUITING

Lux Med Onkologia Sp. z o.o.

Warsaw, Poland

RECRUITING

Wojskowy Instytut Medyczny Państwowy Instytut Badawczy

Warsaw, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wroclaw, Poland

RECRUITING

Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.

Zielona Góra, Poland

COMPLETED

MeSH Terms

Conditions

Primary Myelofibrosis; Neoplasm Metastasis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Head of Clinical Operations

CONTACT

48 123140200; clinicaltrials@ryvu.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 2, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); PL (13)