Trial Title:
Safety and Efficacy of RVU120 Combined with Venetoclax for Treatment of Relapsed/Refractory AML
NCT ID:
NCT06191263
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RVU120
Description:
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Arm group label:
RVU120 + Venetoclax
Other name:
SEL120
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering
events that lead to apoptosis
Arm group label:
RVU120 + Venetoclax
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
Detailed 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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Hospitalier Universitaire Grenoble Alpes
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
Claude-Eric Bulabois, Dr
Facility:
Name:
Centre Hospitalier Le Mans
Address:
City:
Le Mans
Zip:
72037
Country:
France
Status:
Recruiting
Contact:
Last name:
Kamel Laribi, Dr
Facility:
Name:
Centre Hospitalier Universitaire De Lille
Address:
City:
Lille
Zip:
59000
Country:
France
Status:
Recruiting
Contact:
Last name:
Laure Goursaud, Dr
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Status:
Recruiting
Contact:
Last name:
Sylvian Garciaz, Dr
Facility:
Name:
Centre Hospitalier Universitaire De Nice
Address:
City:
Nice
Zip:
06200
Country:
France
Status:
Recruiting
Contact:
Last name:
Thomas Cluzeau, Dr
Facility:
Name:
Centre Hospitalier Universitaire De Nimes
Address:
City:
Nîmes
Zip:
30900
Country:
France
Status:
Recruiting
Contact:
Last name:
Stefan Wickenhauser, Dr
Facility:
Name:
Assistance Publique Hopitaux De Paris
Address:
City:
Paris
Zip:
75010
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre Fenaux, Dr
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Zip:
76000
Country:
France
Status:
Recruiting
Contact:
Last name:
Emilie Lemasle-Hue, Dr
Facility:
Name:
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Maria Giannini, Dr
Phone:
+39 0543 739100
Email:
info@irst.emr.it
Contact backup:
Last name:
Maria Giannini, Dr
Facility:
Name:
Azienda Ospedaliero Universitaria Delle Marche
Address:
City:
Ancona
Zip:
60126
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Debora Capelli, Dr
Facility:
Name:
Univerisity of Bologna Policlinico Sant'Orsola
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Cristina Papayannidis, Prof.
Facility:
Name:
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Address:
City:
Brescia
Zip:
25123
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Erika Borlenghi, Dr
Facility:
Name:
Ospedale Vito Fazzi Lecce
Address:
City:
Lecce
Zip:
73100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Nicola Di Renzo, Dr
Facility:
Name:
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Address:
City:
Roma
Zip:
00133
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Adriano Venditti, Prof.
Facility:
Name:
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Address:
City:
Turin
Zip:
10126
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Ernesta Audisio, Dr
Facility:
Name:
MTZ Clinical Research
Address:
City:
Warszawa
Zip:
02-172
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Krzysztof Mądry
Phone:
+48 22 572 59 59
Email:
info@pratia.com
Contact backup:
Last name:
Krzysztof Mądry
Facility:
Name:
Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
Address:
City:
Biała Podlaska
Zip:
21-500
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Piotr Centkowski, Dr
Facility:
Name:
Uniwersyteckie Centrum Kliniczne
Address:
City:
Gdańsk
Zip:
80-214
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Witold Prejzner, Dr
Facility:
Name:
Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu
Address:
City:
Toruń
Zip:
87-100
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Marcin Rymko, Dr
Facility:
Name:
Instytut Hematologii i Transfuzjologii
Address:
City:
Warsaw
Zip:
02-776
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Ewa Lech-Marańda, Prof.
Facility:
Name:
Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
Address:
City:
Warsaw
Zip:
04-141
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Krzysztof Gawroński, Dr
Facility:
Name:
Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
Address:
City:
Wałbrzych
Zip:
58-309
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Aleksandra Butrym, Prof.
Facility:
Name:
Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii
Address:
City:
Wrocław
Zip:
53-439
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Jarosław Dybko, Dr
Facility:
Name:
Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.
Address:
City:
Zielona Góra
Zip:
65-046
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Emilian Snarski, Prof.
Facility:
Name:
Hospital Del Mar
Address:
City:
Barcelona
Zip:
08003
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Sara Garcia Avila, Dr
Facility:
Name:
Hospital De La Santa Creu I Sant Pau
Address:
City:
Barcelona
Zip:
08041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Guadalupe Oñate, Dr
Facility:
Name:
Institut Catala D'oncologia
Address:
City:
Barcelona
Zip:
08908
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Montserrat Arnan Sangerman, Dr
Facility:
Name:
Hospital San Pedro De Alcantara
Address:
City:
Cáceres
Zip:
10002
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Juan Miguel Bergua Burgués, Dr
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Madrid
Zip:
28033
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Adolfo De La Fuente, Dr
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Irene Sanchez Vandillo, Dr
Facility:
Name:
Hospital Universitario Regional De Malaga
Address:
City:
Málaga
Zip:
29010
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Alejandro Luis Contento Gonzalo, Dr
Facility:
Name:
Clinica Universidad De Navarra
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ana Alfonso Pierola, Dr
Facility:
Name:
University Hospital Virgen Del Rocio S.L.
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Jose Antonio Perez Simón, Dr
Facility:
Name:
Hospital Universitario Y Politecnico La Fe
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Pau Montesinos Fernandez, Dr
Start date:
January 5, 2024
Completion date:
September 2026
Lead sponsor:
Agency:
Ryvu Therapeutics SA
Agency class:
Industry
Source:
Ryvu Therapeutics SA
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06191263
