Clinical trial NCT06397313: RVU120 in Patients With Intermediate or High-risk, Primary or Secondary Myelofibrosis
Official title: An Open-Label Clinical Trial of RVU120 as Monotherapy and in Combination With Ruxolitinib in Patients With Intermediate or High-Risk, Primary or Secondary Myelofibrosis (POTAMI-61)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelofibrosis
Keywords: intermediate
high-risk
primary
secondary
Lead sponsor: Ryvu Therapeutics SA
Sponsor class: INDUSTRY
First posted: 2024-05-02
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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 Participants may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years
2. Diagnosis of Primary or Secondary myelofibrosis (MF) according to the revised World Health Organization (WHO) criteria (Arber 2022).
3. Intermediate or high-risk disease.
4. 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.
5. 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).
6. 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.
7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
8. Adequate hematologic function defined as:

   1. absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support)
   2. platelet count ≥50 × 109/L (Cohort 2 and Cohort 3 only)
9. 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).
10. 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.

Exclusion Criteria:

Each participant must not meet any of the following:

1. Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%.
2. Prior history of hematopoietic stem cell transplant.
3. Participation in any other study in which receipt of an investigational new drug occurred within 4 weeks prior to Cycle 1 Day 1.
4. Active known second malignancy with the exception of any of the following:

   1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
   2. Adequately treated Stage I cancer from which the participant is currently in remission and has been in remission for ≥2 years
   3. Low-risk prostate cancer with a Gleason score \<7 and a prostate-specific antigen (PSA) level \<10 ng/mL
   4. Any other cancer from which the participant has been disease-free for ≥3 years.
5. Known or suspected allergy to RVU120 or RUX.
6. Impairment of gastrointestinal function or gastrointestinal disease
7. 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).
8. Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
9. 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.
10. 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.
11. History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett's formula).
12. Known active human immunodeficiency virus (HIV) infection
13. Current active liver disease from any cause
14. Pregnant or lactating females.
15. Any other prior or current medical or psychiatric condition, intercurrent illness, surgical history, physical or electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the Investigator's opinion, could jeopardize participant safety or interfere with the objectives of the study.

Primary outcomes:
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: 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
timeFrame: 12 months
measure: Duration of spleen response
timeFrame: 12 months
measure: Number of participants with leukemic transformation
timeFrame: 12 months
measure: Number of participants with hematological (clinical) improvement
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Incidence and severity of adverse events (AEs)
timeFrame: 12 months
measure: Change in symptom burden
timeFrame: Baseline and week 24
measure: Absolute change in TSS from baseline
timeFrame: Baseline and week 24
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola-Malpighi
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l.
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Biała Podlaska
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr Jana Biziela
city: Chorzów
country: Poland
facility: M2M Med. Sp. z o.o. Sp. j.
city: Gdańsk
country: Poland
facility: Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz
city: Katowice
country: Poland
facility: Pratia Hematologia Sp. z o.o.
city: Kielce
country: Poland
facility: Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie
city: Toruń
country: Poland
facility: Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Warszawa
country: Poland
facility: Lux Med Onkologia Sp. z o.o.
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny Państwowy Instytut Badawczy
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
city: Zielona Góra
country: Poland
facility: Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.
Study officials:
References: