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

NCT06268574 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: RIVER-52
• Study Type: interventional
• Target: 94
• Locations: 4 countries
• Sites: 41

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Complete Remission (CR), with and without measurable residual disease (MRD)

  Rate of CR, CRh, or CRi

  12 months

Secondary Outcomes (11)

• Overall response rate

  12 months

• Duration of response

  12 months

• Progression-free survival

  12 months

• Overall survival

  12 months

• Incidence of Adverse Events (Safety and Tolerability)

  Up to 24 months

Study Arms (1)

RVU120 single agent

EXPERIMENTAL

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

Drug: RVU120

Interventions

RVU120 DRUG

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

Also known as: SEL120

RVU120 single agent

Eligibility Criteria

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

You may qualify if:

• 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:
• WBC \< 30 x 10(9)/L on Day 1 prior to first dose of study drug
• Platelet count \> 10,000/mcL on Day 1 prior to first dose of study drug
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• 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)
• AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
• Total bilirubin ≤ 3 x ULN
• Creatinine clearance (Cockcroft \& Gault formula) ≥ 30 mL/min

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ryvu Therapeutics SA: lead

Study Sites (41)

Centre Hospitalier Universitaire Grenoble Alpes

La Tronche, France

Location

Centre Hospitalier Le Mans

Le Mans, France

Location

Centre Hospitalier Universitaire de Lille (CHU Lille)

Lille, France

Location

Institut Paoli Calmettes (IPC)

Marseille, France

Location

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

Nice, France

Location

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

Nîmes, France

Location

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

Paris, France

Location

UNICANCER - Centre Henri-Becquerel

Rouen, France

Location

Azienda Ospedaliero Universitaria Delle Marche

Ancona, 60126, Italy

Location

Univerisity of Bologna Policlinico Sant'Orsola

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, 25123, Italy

Location

Careggi University Hospital

Florence, 50134, Italy

Location

Ospedale Vito Fazzi Lecce

Lecce, 73100, Italy

Location

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

Meldola, 47014, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Roma, 00133, Italy

Location

Humanitas Mirasole S.p.A.

Rozzano, 20089, Italy

Location

Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino

Turin, 10126, Italy

Location

MTZ Clinical Research

Warsaw, Mazowieckie Województwo, 02-172, Poland

Location

Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej

Biała Podlaska, 21-500, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

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

Gliwice, 44-102, Poland

Location

Pratia Hematologia Sp. z o.o.

Katowice, 40-519, Poland

Location

Szpital Wojewodzki Im. Dr. Ludwika Rydygiera w Suwalkach

Suwałki, 16-400, Poland

Location

MICS Centrum Medyczne Toruń

Torun, 87-100, Poland

Location

Instytut Hematologii I Transfuzjologii

Warsaw, 02-776, Poland

Location

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Warsaw, 04-141, Poland

Location

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Wałbrzych, 58-309, Poland

Location

Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii

Wroclaw, 53-439, Poland

Location

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

Zielona Góra, 65-046, Poland

Location

Hospital de la Santa Creu i de Sant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Institut Catala d'Oncologia Hospitalet

Barcelona, Spain

Location

Complejo Hospitalario De Caceres - Hospital General San Pedro De Alcantara

Cáceres, Spain

Location

Hospital Universitario La Paz (HULP)

Madrid, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Virgen del Rocío University Hospital

Seville, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: February 20, 2024
• Study Start: January 23, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (11); FR (8); ES (10); PL (12)