Seguridad y eficacia de RVU120 combinado con Venetoclax para el tratamiento de la leucemia mieloide aguda en recaída o refractaria (RIVER-81)
Un ensayo clínico multicéntrico, abierto y de búsqueda de dosis para evaluar la seguridad, farmacocinética, farmacodinamia y eficacia clínica de RVU120 en combinación con Venetoclax en participantes con leucemia mieloide aguda que fracasaron en el tratamiento previo con Ventoclax y un agente hipometilante
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
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Head of Clinical Operations
- Número de teléfono: +48-12 -314-02-00
- Correo electrónico: clinicaltrials@ryvu.com
Ubicaciones de estudio
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Barcelona, España, 08003
- Reclutamiento
- Hospital Del Mar
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Contacto:
- Sara Garcia Avila, Dr
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Investigador principal:
- Sara Garcia Avila, Dr
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Barcelona, España, 08908
- Aún no reclutando
- Institut Catala D'oncologia
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Contacto:
- Montserrat Arnan Sangerman, Dr
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Investigador principal:
- Montserrat Arnan Sangerman, Dr
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Barcelona, España, 08041
- Reclutamiento
- Hospital De La Santa Creu I Sant Pau
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Contacto:
- Guadalupe Oñate, Dr
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Investigador principal:
- Guadalupe Oñate, Dr
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Cáceres, España, 10002
- Reclutamiento
- Hospital San Pedro De Alcantara
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Contacto:
- Juan Miguel Bergua Burgués, Dr
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Investigador principal:
- Juan Miguel Bergua Burgués, Dr
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Madrid, España, 28046
- Reclutamiento
- Hospital Universitario La Paz
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Contacto:
- Irene Sanchez Vandillo, Dr
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Investigador principal:
- Irene Sanchez Vandillo, Dr
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Madrid, España, 28033
- Reclutamiento
- MD Anderson Cancer Center
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Contacto:
- Adolfo De La Fuente, Dr
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Investigador principal:
- Adolfo De La Fuente, Dr
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Málaga, España, 29010
- Reclutamiento
- Hospital Universitario Regional De Malaga
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Contacto:
- Alejandro Luis Contento Gonzalo, Dr
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Investigador principal:
- Alejandro Luis Contento Gonzalo, Dr
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Pamplona, España, 31008
- Reclutamiento
- Clinica Universidad De Navarra
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Contacto:
- Ana Alfonso Pierola, Dr
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Investigador principal:
- Ana Alfonso Pierola, Dr
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Seville, España, 41013
- Reclutamiento
- University Hospital Virgen Del Rocio S.L.
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Contacto:
- Jose Antonio Perez Simón, Dr
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Investigador principal:
- Jose Antonio Perez Simón, Dr
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Valencia, España, 46026
- Reclutamiento
- Hospital Universitario Y Politecnico La Fe
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Contacto:
- Pau Montesinos Fernandez, Dr
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Investigador principal:
- Pau Montesinos Fernandez, Dr
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Grenoble, Francia, 38043
- Reclutamiento
- Centre Hospitalier Universitaire Grenoble Alpes
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Contacto:
- Claude-Eric Bulabois, Dr
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Investigador principal:
- Claude-Eric Bulabois, Dr
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Le Mans, Francia, 72037
- Reclutamiento
- Centre Hospitalier Le Mans
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Investigador principal:
- Kamel Laribi, Dr
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Contacto:
- Kamel Laribi, Dr
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Lille, Francia, 59000
- Reclutamiento
- Centre Hospitalier Universitaire De Lille
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Contacto:
- Laure Goursaud, Dr
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Investigador principal:
- Laure Goursaud, Dr
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Marseille, Francia, 13009
- Reclutamiento
- Institut Paoli-Calmettes
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Contacto:
- Sylvian Garciaz, Dr
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Investigador principal:
- Sylvian Garciaz, Dr
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Nice, Francia, 06200
- Reclutamiento
- Centre Hospitalier Universitaire De Nice
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Contacto:
- Thomas Cluzeau, Dr
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Investigador principal:
- Thomas Cluzeau, Dr
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Nîmes, Francia, 30900
- Reclutamiento
- Centre Hospitalier Universitaire De Nimes
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Investigador principal:
- Stefan Wickenhauser, Dr
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Contacto:
- Stefan Wickenhauser, Dr
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Paris, Francia, 75010
- Reclutamiento
- Assistance Publique Hopitaux De Paris
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Contacto:
- Pierre Fenaux, Dr
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Investigador principal:
- Pierre Fenaux, Dr
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Rouen, Francia, 76000
- Reclutamiento
- Centre Henri Becquerel
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Contacto:
- Emilie Lemasle-Hue, Dr
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Investigador principal:
- Emilie Lemasle-Hue, Dr
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Ancona, Italia, 60126
- Reclutamiento
- Azienda Ospedaliero Universitaria Delle Marche
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Contacto:
- Debora Capelli, Dr
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Investigador principal:
- Debora Capelli, Dr
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Bologna, Italia, 40138
- Reclutamiento
- Univerisity of Bologna Policlinico Sant'Orsola
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Contacto:
- Cristina Papayannidis, Prof.
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Investigador principal:
- Cristina Papayannidis, Prof.
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Brescia, Italia, 25123
- Reclutamiento
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
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Contacto:
- Erika Borlenghi, Dr
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Investigador principal:
- Erika Borlenghi, Dr
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Lecce, Italia, 73100
- Reclutamiento
- Ospedale Vito Fazzi Lecce
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Contacto:
- Nicola Di Renzo, Dr
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Investigador principal:
- Nicola Di Renzo, Dr
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Ravenna, Italia
- Reclutamiento
- AUSL Romagna - Ospedale S.M. Delle Croci
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Investigador principal:
- Giovanni Marconi, Prof.
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Roma, Italia, 00133
- Reclutamiento
- Azienda Ospedaliera Policlinico Universitario Tor Vergata
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Contacto:
- Adriano Venditti, Prof.
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Investigador principal:
- Adriano Venditti, Prof.
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Rozzano, Italia
- Reclutamiento
- Istituto Clinico Humanitas
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Investigador principal:
- Matteo Della Porta, Prof.
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Turin, Italia, 10126
- Reclutamiento
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
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Contacto:
- Ernesta Audisio, Dr
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Investigador principal:
- Ernesta Audisio, Dr
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Forlì-Cesena
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Meldola, Forlì-Cesena, Italia, 47014
- Reclutamiento
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
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Contacto:
- Maria Giannini, Dr
- Número de teléfono: +39 0543 739100
- Correo electrónico: info@irst.emr.it
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Investigador principal:
- Maria Giannini, Dr
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Biała Podlaska, Polonia, 21-500
- Terminado
- Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
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Gdansk, Polonia, 80-214
- Reclutamiento
- Uniwersyteckie Centrum Kliniczne
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Investigador principal:
- Witold Prejzner, Dr
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Contacto:
- Witold Prejzner, Dr
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Katowice, Polonia
- Reclutamiento
- PRATIA Onkologia Katowice
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Investigador principal:
- Sebastian Grosicki, Prof.
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Torun, Polonia, 87-100
- Terminado
- Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu
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Warsaw, Polonia, 02-776
- Reclutamiento
- Instytut Hematologii i Transfuzjologii
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Contacto:
- Ewa Lech-Marańda, Prof.
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Investigador principal:
- Ewa Lech-Marańda, Prof.
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Warsaw, Polonia, 04-141
- Terminado
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
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Wałbrzych, Polonia, 58-309
- Reclutamiento
- Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
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Contacto:
- Aleksandra Butrym, Prof.
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Investigador principal:
- Aleksandra Butrym, Prof.
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Wroclaw, Polonia, 53-439
- Reclutamiento
- Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii
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Contacto:
- Jarosław Dybko, Dr
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Investigador principal:
- Jarosław Dybko, Dr
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Zielona Góra, Polonia, 65-046
- Terminado
- Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.
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Mazowieckie Województwo
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Warsaw, Mazowieckie Województwo, Polonia, 02-172
- Reclutamiento
- MTZ Clinical Research
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Contacto:
- Krzysztof Mądry
- Número de teléfono: +48 22 572 59 59
- Correo electrónico: info@pratia.com
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Investigador principal:
- Krzysztof Mądry
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Patients must have a diagnosis of AML (per 2022 WHO classification)
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Patients must have relapsed or refractory AML (per ELN 2022 criteria)
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Patients must have failed first-line treatment with venetoclax combined with a hypomethylating agent
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Patients must have no alternative therapeutic options likely to produce clinical benefit
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Patients must have ECOG performance status of 0 to 2
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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
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Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures
Exclusion Criteria:
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APL (acute promyelocytic leukemia), the M3 subtype of AML
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Active CNS (central nervous system) leukemia
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Previous treatment with CDK8 and/or CDK19-targeted therapy
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Major surgery within 28 days prior to the first dose of study drug
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Hematopoietic stem cell transplant within 120 days prior to the first dose of study drug
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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
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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)
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Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RVU120 and/or venetoclax
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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
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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)
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Known allergy or hypersensitivity to any component of RVU120 or venetoclax formulations
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 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 |
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19
Otros nombres:
Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering events that lead to apoptosis |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
(Part 1) recommended doses of RVU120 and venetoclax for further study
Periodo de tiempo: approx. 12 months
|
Incidence and severity of toxicities and number of dose limiting toxicities per dose cohort |
approx. 12 months
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(Parts 2 & 3) CR/CRh rate (Complete Remission/Complete Remission with incomplete Hematologic Recovery)
Periodo de tiempo: approx. 36 months
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence and severity of adverse events (safety and tolerability)
Periodo de tiempo: approx. 36 months
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Number and grade of adverse events assessed by CTCAE v5.0 |
approx. 36 months
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Duration of response
Periodo de tiempo: approx. 36 months
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Time from randomization to disease progression or death in patients who achieve CR/CRh |
approx. 36 months
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Post baseline transfusion independence rate
Periodo de tiempo: approx. 36 months
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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
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|
Progression-free survival
Periodo de tiempo: approx. 36 months
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Time from randomization until first evidence of disease progression or death |
approx. 36 months
|
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Relapse-free survival
Periodo de tiempo: approx. 36 months
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Number of participants alive without relapse |
approx. 36 months
|
|
Overall survival
Periodo de tiempo: approx. 36 months
|
Time from randomization to death |
approx. 36 months
|
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Percentage of patients bridged to hematopoietic stem cell transplantation
Periodo de tiempo: approx. 36 months
|
Number of hematopoietic stem cell transplantations following response |
approx. 36 months
|
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(Parts 2 & 3) Impact of treatment on HM-PRO (hematologic malignancy specific patient reported outcome measure)
Periodo de tiempo: approx. 36 months
|
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
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- RIVER-81
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .