Safety and Efficacy of RVU120 Combined With Venetoclax for Treatment of Relapsed/Refractory AML

NCT06191263 | Recruiting Phase 2 DMC

• 1 other identifier: RIVER-81
• Study Type: interventional
• Target: 98
• Locations: 4 countries
• Sites: 37

Brief Summary

The goal of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of RVU120 when administered in combination with venetoclax to adult patients with acute myeloid leukemia (AML) who are relapsed or refractory to prior therapy with venetoclax and a hypomethylating agent. The study consists of three parts. Part 1 aims to identify the doses of RVU120 and venetoclax that are considered to be safe and tolerated. Part 2 will assess the safety and efficacy of the doses selected. And Part 3 is a confirmatory cohort where patients will be treated at the same doses assessed in Part 2

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• (Part 1) recommended doses of RVU120 and venetoclax for further study

  Incidence and severity of toxicities and number of dose limiting toxicities per dose cohort

  approx. 12 months

• (Parts 2 & 3) CR/CRh rate (Complete Remission/Complete Remission with incomplete Hematologic Recovery)

  Preliminary efficacy of RVU120 combined with venetoclax to recommended doses from Part 1. A response of CRh is defined as bone marrow with \<5% blasts, peripheral blood neutrophil count \>0.5 x 10(3)/mcL, and peripheral blood platelet count of \>0.5 x 10(5)/mcL

  approx. 36 months

Secondary Outcomes (8)

• Incidence and severity of adverse events (safety and tolerability)

  approx. 36 months

• Duration of response

  approx. 36 months

• Post baseline transfusion independence rate

  approx. 36 months

• Progression-free survival

  approx. 36 months

• Relapse-free survival

  approx. 36 months

Study Arms (1)

RVU120 + Venetoclax

EXPERIMENTAL

RVU120 oral capsule, 125 or 250 mg administered every other day on Days 1-13 of each 21-day cycle of treatment, combined with venetoclax oral tablet, 200 or 400 mg administered once daily on Days 1-14 of each 21-day cycle of treatment

Drug: RVU120; Drug: Venetoclax

Interventions

RVU120 DRUG

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

Also known as: SEL120

RVU120 + Venetoclax

Venetoclax DRUG

Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering events that lead to apoptosis

RVU120 + Venetoclax

Eligibility Criteria

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

You may qualify if:

• Patients must have a diagnosis of AML (per 2022 WHO classification)
• Patients must have relapsed or refractory AML (per ELN 2022 criteria)
• Patients must have failed first-line treatment with venetoclax combined with a hypomethylating agent
• Patients must 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 \< 25 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
• AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
• Total bilirubin ≤ 3 x ULN
• Creatinine clearance (Cockcroft \& Gault formula) ≥ 50 mL/min
• LVEF (left ventricular ejection fraction) ≥ 40% by electrocardiography
• Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures

You may not qualify if:

• APL (acute promyelocytic leukemia), the M3 subtype of AML
• Active CNS (central nervous system) leukemia
• Previous treatment with CDK8 and/or CDK19-targeted therapy
• Major surgery within 28 days prior to the first dose of study drug
• Hematopoietic stem cell transplant within 120 days prior to the first dose of study drug
• Currently pregnant or breast-feeding. Females of child bearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug
• Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes but is not limited to:
• Active, Grade ≥2 acute GVHD (graft versus host disease) or requirement for systemic immunosuppressive medication for GVHD
• Evidence of ongoing or uncontrolled systemic bacterial, fungal or viral infection and acute inflammatory conditions (including pancreatitis)
• Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active hepatitis, or chronic persistent hepatitis B and/or hepatitis C
• Ongoing drug-induced pneumonitis
• Significant cardiac dysfunction, defined as myocardial infarction within 12 months prior to the first dose of study drug, NYHA (New York Heart Association) Class III or IV heart failure, uncontrolled dysrhythmias, poorly controlled angina
• History of ventricular arrhythmia or QTc ≥ 470 ms (Bazett's formula)
• Prior history of malignancies other than AML, unless disease-free for 5 years or more or prior basal cell carcinoma of the skin, non-metastatic squamous cell carcinoma of the skin, carcinoma in situ of cervix, breast or bladder, and incidental histological finding of prostate cancer (TMN stage T1a or T1b)
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RVU120 and/or venetoclax

Sponsors & Collaborators

• Ryvu Therapeutics SA: lead

Study Sites (37)

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, 38043, France

RECRUITING

Centre Hospitalier Le Mans

Le Mans, 72037, France

RECRUITING

Centre Hospitalier Universitaire De Lille

Lille, 59000, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

RECRUITING

Centre Hospitalier Universitaire De Nice

Nice, 06200, France

RECRUITING

Centre Hospitalier Universitaire De Nimes

Nîmes, 30900, France

RECRUITING

Assistance Publique Hopitaux De Paris

Paris, 75010, France

RECRUITING

Centre Henri Becquerel

Rouen, 76000, France

RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forlì-Cesena, 47014, Italy

RECRUITING

Azienda Ospedaliero Universitaria Delle Marche

Ancona, 60126, Italy

RECRUITING

Univerisity of Bologna Policlinico Sant'Orsola

Bologna, 40138, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, 25123, Italy

RECRUITING

Ospedale Vito Fazzi Lecce

Lecce, 73100, Italy

RECRUITING

AUSL Romagna - Ospedale S.M. Delle Croci

Ravenna, Italy

RECRUITING

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Roma, 00133, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, Italy

RECRUITING

Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino

Turin, 10126, Italy

RECRUITING

MTZ Clinical Research

Warsaw, Mazowieckie Województwo, 02-172, Poland

RECRUITING

Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej

Biała Podlaska, 21-500, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

RECRUITING

PRATIA Onkologia Katowice

Katowice, Poland

RECRUITING

Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu

Torun, 87-100, Poland

RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

RECRUITING

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Warsaw, 04-141, Poland

RECRUITING

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Wałbrzych, 58-309, Poland

RECRUITING

Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii

Wroclaw, 53-439, Poland

RECRUITING

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

Zielona Góra, 65-046, Poland

RECRUITING

Hospital Del Mar

Barcelona, 08003, Spain

RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

RECRUITING

Institut Catala D'oncologia

Barcelona, 08908, Spain

NOT YET RECRUITING

Hospital San Pedro De Alcantara

Cáceres, 10002, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, 28033, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Regional De Malaga

Málaga, 29010, Spain

RECRUITING

Clinica Universidad De Navarra

Pamplona, 31008, Spain

RECRUITING

University Hospital Virgen Del Rocio S.L.

Seville, 41013, Spain

RECRUITING

Hospital Universitario Y Politecnico La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Head of Clinical Operations

CONTACT

+48-538-898-766; clinicaltrials@ryvu.com

Study Design

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

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 5, 2024
• Study Start: January 5, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 13, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10); IT (9); PL (10); FR (8)