POTAMI-61

POTAMI-61 

ClinicalTrials.gov ID NCT06397313 

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 population:

Women and men 18 Years and older 

Study design:

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 Participants may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator. 

Intervention/treatment:

RVU120, Ruxolitinib 

 

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 scores 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: absolute neutrophil count (ANC) ≥1.0 × 109/L (without growth factor support) 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. 
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:

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 antibiotics, 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, 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.
11. History of ventricular arrhythmia, or QTc ≥470 millisecond (Bazett 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. 

 

Participation criteria are verified by the Investigator. Participation in the study is contingent upon meeting all inclusion criteria and meeting none of the exclusion criteria. The criteria provided may not be a complete list. 

 

 

Contact and locations:

Main Researcher	Institution	Address	Phone	Email	Status
Giuseppe Palumbo, Prof.	Azienda Ospedaliero Universitaria Policlinico “G. Rodolico – San Marco”	Via Santa Sofia 7 Catania, Italy			active
Francesca Palandri, Prof.	Policlinico Sant’Orsola-Malpighi	Via Giuseppe Massarenti 9 Bologna, Italy			active
Domenico Russo, Prof.	Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia	Piazzale Spedali Civili 1 Brescia, Italy			non-active
Alessandro Lucchesi, MD PhD	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l.	Via Piero Maroncelli 40 Meldola, Italy			non-active
Barbara Mora, MD PhD	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Via Francesco Sforza 28 Milano, Italy		[email protected]	active
Piotr Centkowski, MD PhD	Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej	ul. Terebelska 57-65 Biała Podlaska, Poland	+48 603 314 074	[email protected]	active
Jarosław Czyż, Prof.	Szpital Uniwersytecki nr 2 im. dr Jana Biziela	ul. Kornela Ujejskiego 75 Bydgoszcz, Poland			non-active
Witold Prejzner, MD PhD	Centrum Wsparcia Badań Klinicznych UCK Ośrodek Badań Klinicznych Wczesnych Faz	ul. Mariana Smoluchowskiego 17 Gdańsk, Poland	+48 58 584 44 66	[email protected]	active
Katarzyna Dulik, MD	M2M Med. Sp. z o.o. Sp. j.	ul. Lwowska 34 Chorzów, Poland	+48 601 414 651	[email protected]	active
Sebastian Grosicki, Prof.	Pratia Hematologia Sp. z o.o.	ul. Tadeusza Kosciuszki 92 Katowice, Poland	+48 501 714 019	[email protected]	active
Paweł Steckiewicz, MD PhD	Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej	ul. Artwińskiego 3 Kielce, Poland	+48 41 367 43 15	[email protected]	non-active
Tomasz Sacha, Prof.	Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie	ul. Macieja Jakubowskiego 2 Krakow, Poland	+48 12 400 32 00	[email protected]	active
Aneta Szudy-Szczyrek, MD PhD	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie	ul. Stanisława Staszica 11 Lublin, Poland			non-active
Marcin Rymko, MD PhD	Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu	ul. św. Józefa 53-59 Toruń, Poland	+48 56 679 3745	[email protected]	active
Joanna Barankiewicz, MD PhD	Lux Med Onkologia Sp. z o.o.	ul. Szamocka 6 Warszawa, Poland			active
Krzysztof Gawroński, MD PhD	Wojskowy Instytut Medyczny Państwowy Instytut Badawczy	ul. Szaserów 128 Warszawa, Poland			active
Tomasz Wróbel, Prof.	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu	ul. Borowska 213 Wrocław, Poland			active
Emilian Snarski, Prof.	Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Górze Sp. z o. o.	ul. Zyty 26 Zielona Góra, Poland			non-active