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

NCT ID: NCT06191263

Last Updated: 2025-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-05

Study Completion Date

2026-09-30

Brief Summary

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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

Detailed Description

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In Part 1 dose-escalation participants will receive escalating oral doses of RVU120 starting at 125 mg administered every other day on days 1-13, and escalating oral doses of venetoclax starting with 200 mg administered daily on days 1-14 of each 21-day cycle of treatment. The recommended doses for further study will be based on the observed safety, tolerance, PK and PD.

In Part 2, it will be assessed whether the recommended dose level from Part 1 reaches the targetted response criteria, and if reached, Part 3 will be initiated to further evaluate the efficacy and safety of the recommended doses in a larger population.

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RVU120 + Venetoclax

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

Group Type EXPERIMENTAL

RVU120

Intervention Type DRUG

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

Venetoclax

Intervention Type DRUG

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

Interventions

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RVU120

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

Intervention Type DRUG

Venetoclax

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

Intervention Type DRUG

Other Intervention Names

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SEL120

Eligibility Criteria

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Inclusion Criteria

* 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:

1. WBC \< 25 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. AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
4. Total bilirubin ≤ 3 x ULN
5. Creatinine clearance (Cockcroft \& Gault formula) ≥ 50 mL/min
6. 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

Exclusion Criteria

* 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:

1. Active, Grade ≥2 acute GVHD (graft versus host disease) or requirement for systemic immunosuppressive medication for GVHD
2. Evidence of ongoing or uncontrolled systemic bacterial, fungal or viral infection and acute inflammatory conditions (including pancreatitis)
3. Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active hepatitis, or chronic persistent hepatitis B and/or hepatitis C
4. Ongoing drug-induced pneumonitis
5. 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
6. History of ventricular arrhythmia or QTc ≥ 470 ms (Bazett's formula)
7. 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
* 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
* Taking any medications, over-the-counter medications, foods or herbal supplements that are known to be strong or moderate inhibitors of CYP3A4 or P-gp (P-glycoprotein)
* Known allergy or hypersensitivity to any component of RVU120 or venetoclax formulations
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ryvu Therapeutics SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, , France

Site Status RECRUITING

Centre Hospitalier Le Mans

Le Mans, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Lille

Lille, , France

Site Status RECRUITING

Institut Paoli-Calmettes

Marseille, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Nice

Nice, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Nimes

Nîmes, , France

Site Status RECRUITING

Assistance Publique Hopitaux De Paris

Paris, , France

Site Status RECRUITING

Centre Henri Becquerel

Rouen, , France

Site Status RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forlì-Cesena, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Delle Marche

Ancona, , Italy

Site Status RECRUITING

Univerisity of Bologna Policlinico Sant'Orsola

Bologna, , Italy

Site Status RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, , Italy

Site Status RECRUITING

Ospedale Vito Fazzi Lecce

Lecce, , Italy

Site Status RECRUITING

AUSL Romagna - Ospedale S.M. Delle Croci

Ravenna, , Italy

Site Status RECRUITING

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Roma, , Italy

Site Status RECRUITING

Istituto Clinico Humanitas

Rozzano, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino

Turin, , Italy

Site Status RECRUITING

MTZ Clinical Research

Warsaw, Mazowieckie Województwo, Poland

Site Status RECRUITING

Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej

Biała Podlaska, , Poland

Site Status RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status RECRUITING

PRATIA Onkologia Katowice

Katowice, , Poland

Site Status RECRUITING

Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu

Torun, , Poland

Site Status RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status RECRUITING

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Warsaw, , Poland

Site Status RECRUITING

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Wałbrzych, , Poland

Site Status RECRUITING

Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii

Wroclaw, , Poland

Site Status RECRUITING

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

Zielona Góra, , Poland

Site Status RECRUITING

Hospital Del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Institut Catala D'oncologia

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital San Pedro De Alcantara

Cáceres, , Spain

Site Status RECRUITING

MD Anderson Cancer Center

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Regional De Malaga

Málaga, , Spain

Site Status RECRUITING

Clinica Universidad De Navarra

Pamplona, , Spain

Site Status RECRUITING

University Hospital Virgen Del Rocio S.L.

Seville, , Spain

Site Status RECRUITING

Hospital Universitario Y Politecnico La Fe

Valencia, , Spain

Site Status RECRUITING

Countries

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France Italy Poland Spain

Central Contacts

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Head of Clinical Operations

Role: CONTACT

+48-538-898-766

Facility Contacts

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Claude-Eric Bulabois, Dr

Role: primary

Kamel Laribi, Dr

Role: primary

Laure Goursaud, Dr

Role: primary

Sylvian Garciaz, Dr

Role: primary

Thomas Cluzeau, Dr

Role: primary

Stefan Wickenhauser, Dr

Role: primary

Pierre Fenaux, Dr

Role: primary

Emilie Lemasle-Hue, Dr

Role: primary

Maria Giannini, Dr

Role: primary

+39 0543 739100

Debora Capelli, Dr

Role: primary

Cristina Papayannidis, Prof.

Role: primary

Erika Borlenghi, Dr

Role: primary

Nicola Di Renzo, Dr

Role: primary

Adriano Venditti, Prof.

Role: primary

Ernesta Audisio, Dr

Role: primary

Krzysztof Mądry

Role: primary

+48 22 572 59 59

Piotr Centkowski, Dr

Role: primary

Witold Prejzner, Dr

Role: primary

Marcin Rymko, Dr

Role: primary

Ewa Lech-Marańda, Prof.

Role: primary

Krzysztof Gawroński, Dr

Role: primary

Aleksandra Butrym, Prof.

Role: primary

Jarosław Dybko, Dr

Role: primary

Emilian Snarski, Prof.

Role: primary

Sara Garcia Avila, Dr

Role: primary

Guadalupe Oñate, Dr

Role: primary

Montserrat Arnan Sangerman, Dr

Role: primary

Juan Miguel Bergua Burgués, Dr

Role: primary

Adolfo De La Fuente, Dr

Role: primary

Irene Sanchez Vandillo, Dr

Role: primary

Alejandro Luis Contento Gonzalo, Dr

Role: primary

Ana Alfonso Pierola, Dr

Role: primary

Jose Antonio Perez Simón, Dr

Role: primary

Pau Montesinos Fernandez, Dr

Role: primary

Other Identifiers

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RIVER-81

Identifier Type: -

Identifier Source: org_study_id

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