RIVER-52

RIVER-52

ClinicalTrials.gov ID NCT06268574 

Title:

Multicenter, open-label clinical trial of RVU120 in patients with relapsed or refractory high-risk myelodysplastic syndrome or acute myeloid leukemia with or without NPM1 mutation (RIVER-52)

Study population:

Women and man 18 Years and older

Study design:

Patients entering the study will undergo a Screening Period of up to 21 days, a Treatment Period where they will take the drug every other day (7 times in 13 days) in cycles of 21 days, an End of Treatment period (lasting approximately 30 days after last dose), and a 1-year Follow-up Period where participants will be contacted every 3 months for progression and survival status.

Intervention/treatment:

RVU120

 

Eligibility criteria: 

Inclusion Criteria

1. Subjects must sign a written informed consent document and complete study related procedures
2. Patients must have a diagnosis of AML or HR-MDS (per 2022 WHO classification) with MDS confirmed as high risk with IPSS-R
3. Patients must have relapsed or refractory AML (per ELN 2022 criteria)
4. Patients must have relapsed or progressing HR-MDS (per IWG response criteria)
5. Patients must have failed first-line treatment and have no alternative therapeutic options likely to produce clinical benefit
6. Patients must have ECOG performance status of 0 to 2
7. Patients must have adequate end organ function defined as:
   1. WBC < 30 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. Serum albumin ≥ 25 g/L (2.5 g/dL)
   4. 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)
   5. AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 x ULN (upper limit of normal)
   6. Total bilirubin ≤ 3 x ULN
   7. Creatinine clearance (Cockcroft & Gault formula) ≥ 30 mL/min

Exclusion Criteria

1. Active central nervous system (CNS) leukemia.
2. Diagnosis of acute promyelocytic leukemia (APL), the M3 subtype of AML.
3. Previous treatment with CDK8 and/or CDK19-targeted therapy.
4. Major surgery within 28 days prior to first dose of study drug.
5. Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
6. Active, ≥Grade 2 acute graft versus host disease (GVHD), active moderate-to-severe chronic GVHD, or requirement for systemic immunosuppressive medications for GVHD
7. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis).
8. Known seropositivity or history of active viral infection with human immunodeficiency virus (HIV).
9. Ongoing significant liver disease
10. Impairment of gastrointestinal function or gastrointestinal disease
11. Ongoing drug-induced pneumonitis.
12. Concurrent participation in another investigational clinical trial.
13. Taking any medications, herbal supplements, or other substances (including smoking) that may interfere with the metabolism of the study drug
14. 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.
15. History of ventricular arrhythmia, or QTc ≥470 ms (Bazett’s formula).
16. Prior history of malignancies other than AML, unless the participant has been free of the disease for 5 years or more prior to Screening
17. Pregnant or breast-feeding.

Participation criteria are verified by the investigator. Participation in the study is contingent upon meeting all inclusion criteria and meeting none of the exclusion criteria. The criteria provided may not be a complete list.  

 

Contact and locations:

Main Researcher	Institution	Address	Phone	Email	Status
Krzysztof Mądry, MD PhD	MTZ Clinical Research Research powered by Pratia	ul. Gładka 22 Warszawa, Poland	+48 669494678	[email protected]
Krzysztof Gawroński, MD PhD	Wojskowy Instytut Medyczny – Państwowy Instytut Badawczy	ul. Szaserów 128  Warszawa, Poland	+48 261817013	[email protected]
Aleksandra Butrym, Prof.	Specjalistyczny Szpital im. Dr A. Sokołowskiego w Wałbrzychu	ul. Sokołowskiego 4 Wałbrzych, Poland	+48 746489736	[email protected]
Piotr Centkowski, MD PhD	KO-MED Nova Sp. z o.o. Ośrodek Badań Klinicznych w Białej Podlaskiej	ul. Terebelska 57-65 Biała Podlaska, Poland	+48 603314074, +48 833067700	[email protected], [email protected]
Jarosław Dybko, MD PhD	Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii we Wrocławiu	ul. Grabiszyńska 105 Wrocław, Poland	+48 782999717	[email protected]
Witold Prejzner, MD PhD	Uniwersyteckie Centrum Kliniczne, Klinika Hematologii   i Transplantologii	ul. Smoluchowskiego 17 Gdańsk, Poland	+48 585844340	[email protected]
Małgorzata Krawczyk-Kuliś, Prof.	Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie	ul. Wybrzeże Armii Krajowej 15 Gliwice, Poland	+48 322788559	[email protected]
Dominik Chraniuk, MD PhD	MICS Centrum Medyczne Toruń	ul. Batorego 18-22 Toruń, Poland	+48 662062410	[email protected]
Ewa Lech-Marańda, Prof.	Instytut Hematologii i Transplantologii	ul. Indiry Gandhi 14 Warszawa, Poland
Emilian Snarski, Prof.	Szpital Uniwersytecki im. Karola Marcinkowskiego	ul. Zyty 26 Zielona Góra, Poland	+48 683296371	m.g[email protected]
Alina Urbanowicz, Prof.	Szpital Wojewódzki im. Ludwika Rydygiera	ul. Szpitalna 60 Suwałki, Poland	+48 875629521	[email protected] [email protected]
Sebastian Grosicki, Prof.	Pratia Onkologia Katowice	ul. Tadeusza Kościuszki 92   Katowice, Poland	+48 501714019	[email protected]
Adriano Venditti, Prof.	Universita Degli Studi di Roma “Tor Vergata” – Facolta di Medicina e Chirurgia	Viale Oxford, 81 Rome, Italy
Cristina Papayannidis, MD PhD	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Via Giuseppe Massarenti 9 padiglione 8 Bologna, Italy
Valeria Santini, MD PhD	Azienda Ospedaliero-Universitaria Careggi	Largo Brambilla 3 Florence, Italy
Maria Benedetta Giannini, MD PhD	Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.	Via Piero Maroncelli 40 Meldola, Italy	+39 0543739100	[email protected]
Erika Borlenghi, MD PhD	Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia	Piazzale Spedali Civili 1 Brescia, Italy
Matteo Giovanni Della Porta, Prof.	Humanitas Mirasole S.p.A.	Via Alessandro Manzoni 56 Rozzano, Italy
Ernesta Audisio, MD PhD	Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino	Corso Bramante 88 Turin, Italy
Sara Galimberti, MD PhD	Azienda Ospedaliero Universitaria Pisana	Via Roma 67 Pisa, Italy
Debora Capelli, MD PhD	Azienda Ospedaliero Universitaria Delle Marche	Via Conca 71 Ancona, Italy
Nicola Di Renzo, MD PhD	Ospedale Vito Fazzi Lecce	Piazza Filippo Muratore 1 Lecce, Italy
Roberto Cairoli, Prof.	ASST Grande Ospedale Metropolitano Niguarda	Piazza Dell’ospedale Maggiore 3 Milan, Italy
Michaela Rondoni, MD PhD	“S. Maria delle Croci” Hospital Oncology and Haematology Department
Pau Montesinos Fernández, MD PhD	Hospital Universitario Y Politecnico La Fe	Avenida De Fernando Abril Martorell 106 Valencia, Spain
Montserrat Arnan Sangerman, MD PhD	Institut Catala D’oncologia	Avinguda De La Gran Via De L’hospitalet 199-203 Llobregat, Spain
José Antonio Pérez Simón, MD PhD	University Hospital Virgen Del Rocio S.L.	Avenida De Manuel Siurot S/n Sevilla, Spain
Juan Miguel Bergua Burgues, MD PhD	Hospital San Pedro De Alcantara	Avenida De Pablo Naranjo Porras S/n Caceres, Spain
Sylvain Garciaz, MD PhD	Institut Paoli-Calmettes	232 Boulevard De Sainte Marguerite Marseille, France
Stefan Wickenhauser, MD PhD	Centre Hospitalier Universitaire De Nimes	Place Du Professeur Robert Debre Nimes, France
Claude-Eric Bulabois, MD PhD	Centre Hospitalier Universitaire Grenoble Alpes	Boulevard De La Chantourne Grenoble, France
Kamel Laribi, MD PhD	Centre Hospitalier Le Mans	194 Avenue Rubillard Le Mans, France
Laure Goursaud, MD PhD	Centre Hospitalier Universitaire De Lille	Rue Michel Polonowski Lille, France
Emilie Lemasle Hue, MD PhD	Centre Henri Becquerel	1 Rue D Amiens Rouen, France
Thomas Cluzeau, MD PhD	Centre Hospitalier Universitaire De Nice	151 Route De Saint Antoine Nice, France
Pierre Fenaux, MD PhD	Assistance Publique Hopitaux De Paris	1 Avenue Claude Vellefaux Paris, France