Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AML

NCT ID: NCT06268574

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-23
• Study Completion Date: 2026-09-30

Brief Summary

The goal of this study is to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of the agent RVU120 when administered to adult patients with relapsed or refractory acute myeloid leukemia (AML) or relapsed or progressing high-risk myelodysplastic syndrome (HR-MDS) and who have no alternative therapies available. The study consists of two parts. Part 1 will assess the safety and tolerability of the dosages given and the level of anti-tumor activity or clinical response. Based on the results from part 1 the study will continue to enrol patient into Part 2 which will continue to evaluate safety and tolerability and anti-tumor activity in a larger number of patients.

Detailed Description

Patients entering the study will undergo a Screening Period of up to 21 days, a Treatment Period where they will take the drug every other day (7 times in 13 days) in cycles of 21 days, an End of Treatment period (lasting approximately 30 days after last dose), and a 1-year Follow-up Period where participants will be contacted every 3 months for progression and survival status. In Part 1, patients with AML or HR-MDS will be enrolled. All patients will receive RVU120 until the patient meets eligibility for transplant, until there is disease progression or if there are signs of intolerance. A patient may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator. Depending on the outcome of part 1, part 2 may include patients with HR-MDS and AML irrespective of NPM1 mutation status.

Conditions

Acute Myeloid Leukemia (AML); High-risk Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RVU120 single agent

RVU120 oral capsules administered at dose of 250 mg every other day on Days 1-13 of each 21-day cycle of treatment.

Group Type: EXPERIMENTAL

RVU120

Intervention Type: DRUG

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

Interventions

RVU120

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

Intervention Type: DRUG

Other Intervention Names

SEL120

Eligibility Criteria

Inclusion Criteria

• Subjects must sign a written informed consent document and complete study related procedures
• Patients must have a diagnosis of AML or HR-MDS (per 2022 WHO classification) with MDS confirmed as high risk with IPSS-R
• Patients must have relapsed or refractory AML (per ELN 2022 criteria)
• Patients must have relapsed or progressing HR-MDS (per IWG response criteria)
• Patients must have failed first-line treatment and have no alternative therapeutic options likely to produce clinical benefit
• Patients must have ECOG performance status of 0 to 2
• Patients must have adequate end organ function defined as:

1. WBC < 30 x 10(9)/L on Day 1 prior to first dose of study drug

2. Platelet count > 10,000/mcL on Day 1 prior to first dose of study drug

3. Serum albumin ≥ 25 g/L (2.5 g/dL)

4. Normal coagulation (elevated international normalized ratio [INR], prothrombin time or activated partial thromboplastin time [APTT] <1.3 x the upper limit of normal [ULN] acceptable)

5. AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)

6. Total bilirubin ≤ 3 x ULN

7. Creatinine clearance (Cockcroft & Gault formula) ≥ 30 mL/min

Exclusion Criteria

• Active central nervous system (CNS) leukemia.
• Diagnosis of acute promyelocytic leukemia (APL), the M3 subtype of AML.
• Previous treatment with CDK8 and/or CDK19-targeted therapy.
• Major surgery within 28 days prior to first dose of study drug.
• Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
• Active, ≥Grade 2 acute graft versus host disease (GVHD), active moderate-to-severe chronic GVHD, or requirement for systemic immunosuppressive medications for GVHD
• Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis).
• Known seropositivity or history of active viral infection with human immunodeficiency virus (HIV).
• Ongoing significant liver disease
• Impairment of gastrointestinal function or gastrointestinal disease
• Ongoing drug-induced pneumonitis.
• Concurrent participation in another investigational clinical trial.
• Taking any medications, herbal supplements, or other substances (including smoking) that may interfere with the metabolism of the study drug
• Significant cardiac dysfunction defined as myocardial infarction within 12 months of first dose of study drug, 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.
• History of ventricular arrhythmia, or QTc ≥470 ms (Bazett's formula).
• Prior history of malignancies other than AML, unless the participant has been free of the disease for 5 years or more prior to Screening
• Pregnant or breast-feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ryvu Therapeutics SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier Universitaire Grenoble Alpes

La Tronche, , France

Centre Hospitalier Le Mans

Le Mans, , France

Centre Hospitalier Universitaire de Lille (CHU Lille)

Lille, , France

Institut Paoli Calmettes (IPC)

Marseille, , France

Centre Hospitalier Universitaire (CHU) de Nice - Hopital L'Archet I

Nice, , France

Centre Hospitalier Universitaire de Nimes (CHU) - Institut de Cancerologie du Gard

Nîmes, , France

Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis

Paris, , France

UNICANCER - Centre Henri-Becquerel

Rouen, , France

Azienda Ospedaliero Universitaria Delle Marche

Ancona, , Italy

Univerisity of Bologna Policlinico Sant'Orsola

Bologna, , Italy

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, , Italy

Careggi University Hospital

Florence, , Italy

Ospedale Vito Fazzi Lecce

Lecce, , Italy

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Meldola, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Roma, , Italy

Humanitas Mirasole S.p.A.

Rozzano, , Italy

Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino

Turin, , Italy

MTZ Clinical Research

Warsaw, Mazowieckie Województwo, Poland

Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej

Biała Podlaska, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Gliwice, , Poland

Pratia Hematologia Sp. z o.o.

Katowice, , Poland

Szpital Wojewodzki Im. Dr. Ludwika Rydygiera w Suwalkach

Suwałki, , Poland

MICS Centrum Medyczne Toruń

Torun, , Poland

Instytut Hematologii I Transfuzjologii

Warsaw, , Poland

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Warsaw, , Poland

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Wałbrzych, , Poland

Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii

Wroclaw, , Poland

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

Zielona Góra, , Poland

Hospital de la Santa Creu i de Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Institut Catala d'Oncologia Hospitalet

Barcelona, , Spain

Complejo Hospitalario De Caceres - Hospital General San Pedro De Alcantara

Cáceres, , Spain

Hospital Universitario La Paz (HULP)

Madrid, , Spain

MD Anderson Cancer Center Madrid

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Virgen del Rocío University Hospital

Seville, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Countries

France; Italy; Poland; Spain

Other Identifiers

RIVER-52

Identifier Type: -

Identifier Source: org_study_id