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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06191263
Other study ID # RIVER-81
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date January 5, 2024
Est. completion date September 2026

Study information

Verified date June 2024
Source Ryvu Therapeutics SA
Contact Head of Clinical Operations
Phone +48-538-898-766
Email clinicaltrials@ryvu.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 98
Est. completion date September 2026
Est. primary completion date February 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
RVU120
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Venetoclax
Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering events that lead to apoptosis

Locations

Country Name City State
France Centre Hospitalier Universitaire Grenoble Alpes Grenoble
France Centre Hospitalier Le Mans Le Mans
France Centre Hospitalier Universitaire De Lille Lille
France Institut Paoli-Calmettes Marseille
France Centre Hospitalier Universitaire De Nice Nice
France Centre Hospitalier Universitaire De Nimes Nîmes
France Assistance Publique Hopitaux De Paris Paris
France Centre Henri Becquerel Rouen
Italy 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 Ospedale Vito Fazzi Lecce Lecce
Italy Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Forlì-Cesena
Italy Azienda Ospedaliera Policlinico Universitario Tor Vergata Roma
Italy Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino Turin
Poland Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej Biala Podlaska
Poland Uniwersyteckie Centrum Kliniczne Gdansk
Poland Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Kielcach Kielce
Poland Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu Torun
Poland Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego Walbrzych
Poland Instytut Hematologii i Transfuzjologii Warsaw
Poland Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy Warsaw
Poland MTZ Clinical Research Warszawa Mazowieckie Województwo
Poland Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii Wroclaw
Poland Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego we Wroclawiu Wroclaw
Poland Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o. Zielona Góra
Spain Hospital De La Santa Creu I Sant Pau Barcelona
Spain Hospital Del Mar Barcelona
Spain Institut Catala D'oncologia Barcelona
Spain Hospital San Pedro De Alcantara Cáceres
Spain Hospital Universitario La Paz Madrid
Spain MD Anderson Cancer Center Madrid
Spain Hospital Universitario Regional De Malaga Málaga
Spain Clinica Universidad De Navarra Pamplona
Spain University Hospital Virgen Del Rocio S.L. Sevilla
Spain Hospital Universitario Y Politecnico La Fe Valencia

Sponsors (1)

Lead Sponsor Collaborator
Ryvu Therapeutics SA

Countries where clinical trial is conducted

France,  Italy,  Poland,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary (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
Primary (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 Incidence and severity of adverse events (safety and tolerability) Number and grade of adverse events assessed by CTCAE v5.0 approx. 36 months
Secondary Duration of response Time from randomization to disease progression or death in patients who achieve CR/CRh approx. 36 months
Secondary Post baseline transfusion independence rate Transfusion independence is defined as a period of 56 days with no transfusion between the first dose of study drug and the last dose of study drug + 30 days. The rate of conversion of red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependent approx. 36 months
Secondary Progression-free survival Time from randomization until first evidence of disease progression or death approx. 36 months
Secondary Relapse-free survival Number of participants alive without relapse approx. 36 months
Secondary Overall survival Time from randomization to death approx. 36 months
Secondary Percentage of patients bridged to hematopoietic stem cell transplantation Number of hematopoietic stem cell transplantations following response approx. 36 months
Secondary (Parts 2 & 3) Impact of treatment on HM-PRO (hematologic malignancy specific patient reported outcome measure) The HM-PRO consists of two scales, Part A (Impact) that measures treatment impact on patient's health-related quality of life using a three-point Likert scale (Not at all, A little, A lot) and Part B (Signs and Symptoms) that captures the severity of disease or treatment related signs and symptoms on a three-point Likert scale (Not at all, Mild, Severe). approx. 36 months
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