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Sikkerhed og effektivitet af RVU120 kombineret med Venetoclax til behandling af recidiverende/refraktær AML (RIVER-81)

15. september 2026 opdateret af: Ryvu Therapeutics SA

Et multicenter, åbent, dosisfindende klinisk forsøg til vurdering af sikkerhed, farmakokinetik, farmakodynamik og klinisk effektivitet af RVU120 i kombination med Venetoclax hos deltagere med akut myeloid leukæmi, som har mislykket tidligere terapi med Ventoclax og et hypomethylerende middel

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

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

98

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Frankrig
      • Grenoble, Frankrig, 38043
        • Rekruttering
        • Centre Hospitalier Universitaire Grenoble Alpes
        • Kontakt:
          • Claude-Eric Bulabois, Dr
        • Ledende efterforsker:
          • Claude-Eric Bulabois, Dr
      • Le Mans, Frankrig, 72037
        • Rekruttering
        • Centre Hospitalier Le Mans
        • Ledende efterforsker:
          • Kamel Laribi, Dr
        • Kontakt:
          • Kamel Laribi, Dr
      • Lille, Frankrig, 59000
        • Rekruttering
        • Centre Hospitalier Universitaire De Lille
        • Kontakt:
          • Laure Goursaud, Dr
        • Ledende efterforsker:
          • Laure Goursaud, Dr
      • Marseille, Frankrig, 13009
        • Rekruttering
        • Institut Paoli-Calmettes
        • Kontakt:
          • Sylvian Garciaz, Dr
        • Ledende efterforsker:
          • Sylvian Garciaz, Dr
      • Nice, Frankrig, 06200
        • Rekruttering
        • Centre Hospitalier Universitaire De Nice
        • Kontakt:
          • Thomas Cluzeau, Dr
        • Ledende efterforsker:
          • Thomas Cluzeau, Dr
      • Nîmes, Frankrig, 30900
        • Rekruttering
        • Centre Hospitalier Universitaire De Nimes
        • Ledende efterforsker:
          • Stefan Wickenhauser, Dr
        • Kontakt:
          • Stefan Wickenhauser, Dr
      • Paris, Frankrig, 75010
        • Rekruttering
        • Assistance Publique Hopitaux De Paris
        • Kontakt:
          • Pierre Fenaux, Dr
        • Ledende efterforsker:
          • Pierre Fenaux, Dr
      • Rouen, Frankrig, 76000
        • Rekruttering
        • Centre Henri Becquerel
        • Kontakt:
          • Emilie Lemasle-Hue, Dr
        • Ledende efterforsker:
          • Emilie Lemasle-Hue, Dr
  • Italien
      • Ancona, Italien, 60126
        • Rekruttering
        • Azienda Ospedaliero Universitaria Delle Marche
        • Kontakt:
          • Debora Capelli, Dr
        • Ledende efterforsker:
          • Debora Capelli, Dr
      • Bologna, Italien, 40138
        • Rekruttering
        • Univerisity of Bologna Policlinico Sant'Orsola
        • Kontakt:
          • Cristina Papayannidis, Prof.
        • Ledende efterforsker:
          • Cristina Papayannidis, Prof.
      • Brescia, Italien, 25123
        • Rekruttering
        • Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
        • Kontakt:
          • Erika Borlenghi, Dr
        • Ledende efterforsker:
          • Erika Borlenghi, Dr
      • Lecce, Italien, 73100
        • Rekruttering
        • Ospedale Vito Fazzi Lecce
        • Kontakt:
          • Nicola Di Renzo, Dr
        • Ledende efterforsker:
          • Nicola Di Renzo, Dr
      • Ravenna, Italien
        • Rekruttering
        • AUSL Romagna - Ospedale S.M. Delle Croci
        • Ledende efterforsker:
          • Giovanni Marconi, Prof.
      • Roma, Italien, 00133
        • Rekruttering
        • Azienda Ospedaliera Policlinico Universitario Tor Vergata
        • Kontakt:
          • Adriano Venditti, Prof.
        • Ledende efterforsker:
          • Adriano Venditti, Prof.
      • Rozzano, Italien
        • Rekruttering
        • Istituto Clinico Humanitas
        • Ledende efterforsker:
          • Matteo Della Porta, Prof.
      • Turin, Italien, 10126
        • Rekruttering
        • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
        • Kontakt:
          • Ernesta Audisio, Dr
        • Ledende efterforsker:
          • Ernesta Audisio, Dr
    • Forlì-Cesena
      • Meldola, Forlì-Cesena, Italien, 47014
        • Rekruttering
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
        • Kontakt:
        • Ledende efterforsker:
          • Maria Giannini, Dr
  • Polen
      • Biała Podlaska, Polen, 21-500
        • Afsluttet
        • Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
      • Gdansk, Polen, 80-214
        • Rekruttering
        • Uniwersyteckie Centrum Kliniczne
        • Ledende efterforsker:
          • Witold Prejzner, Dr
        • Kontakt:
          • Witold Prejzner, Dr
      • Katowice, Polen
        • Rekruttering
        • PRATIA Onkologia Katowice
        • Ledende efterforsker:
          • Sebastian Grosicki, Prof.
      • Torun, Polen, 87-100
        • Afsluttet
        • Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu
      • Warsaw, Polen, 02-776
        • Rekruttering
        • Instytut Hematologii i Transfuzjologii
        • Kontakt:
          • Ewa Lech-Marańda, Prof.
        • Ledende efterforsker:
          • Ewa Lech-Marańda, Prof.
      • Warsaw, Polen, 04-141
        • Afsluttet
        • Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
      • Wałbrzych, Polen, 58-309
        • Rekruttering
        • Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
        • Kontakt:
          • Aleksandra Butrym, Prof.
        • Ledende efterforsker:
          • Aleksandra Butrym, Prof.
      • Wroclaw, Polen, 53-439
        • Rekruttering
        • Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii
        • Kontakt:
          • Jarosław Dybko, Dr
        • Ledende efterforsker:
          • Jarosław Dybko, Dr
      • Zielona Góra, Polen, 65-046
        • Afsluttet
        • Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.
    • Mazowieckie Województwo
      • Warsaw, Mazowieckie Województwo, Polen, 02-172
        • Rekruttering
        • MTZ Clinical Research
        • Kontakt:
        • Ledende efterforsker:
          • Krzysztof Mądry
  • Spanien
      • Barcelona, Spanien, 08003
        • Rekruttering
        • Hospital Del Mar
        • Kontakt:
          • Sara Garcia Avila, Dr
        • Ledende efterforsker:
          • Sara Garcia Avila, Dr
      • Barcelona, Spanien, 08908
        • Ikke rekrutterer endnu
        • Institut Catala D'oncologia
        • Kontakt:
          • Montserrat Arnan Sangerman, Dr
        • Ledende efterforsker:
          • Montserrat Arnan Sangerman, Dr
      • Barcelona, Spanien, 08041
        • Rekruttering
        • Hospital De La Santa Creu I Sant Pau
        • Kontakt:
          • Guadalupe Oñate, Dr
        • Ledende efterforsker:
          • Guadalupe Oñate, Dr
      • Cáceres, Spanien, 10002
        • Rekruttering
        • Hospital San Pedro De Alcantara
        • Kontakt:
          • Juan Miguel Bergua Burgués, Dr
        • Ledende efterforsker:
          • Juan Miguel Bergua Burgués, Dr
      • Madrid, Spanien, 28046
        • Rekruttering
        • Hospital Universitario La Paz
        • Kontakt:
          • Irene Sanchez Vandillo, Dr
        • Ledende efterforsker:
          • Irene Sanchez Vandillo, Dr
      • Madrid, Spanien, 28033
        • Rekruttering
        • MD Anderson Cancer Center
        • Kontakt:
          • Adolfo De La Fuente, Dr
        • Ledende efterforsker:
          • Adolfo De La Fuente, Dr
      • Málaga, Spanien, 29010
        • Rekruttering
        • Hospital Universitario Regional De Malaga
        • Kontakt:
          • Alejandro Luis Contento Gonzalo, Dr
        • Ledende efterforsker:
          • Alejandro Luis Contento Gonzalo, Dr
      • Pamplona, Spanien, 31008
        • Rekruttering
        • Clinica Universidad De Navarra
        • Kontakt:
          • Ana Alfonso Pierola, Dr
        • Ledende efterforsker:
          • Ana Alfonso Pierola, Dr
      • Seville, Spanien, 41013
        • Rekruttering
        • University Hospital Virgen Del Rocio S.L.
        • Kontakt:
          • Jose Antonio Perez Simón, Dr
        • Ledende efterforsker:
          • Jose Antonio Perez Simón, Dr
      • Valencia, Spanien, 46026
        • Rekruttering
        • Hospital Universitario Y Politecnico La Fe
        • Kontakt:
          • Pau Montesinos Fernandez, Dr
        • Ledende efterforsker:
          • Pau Montesinos Fernandez, Dr

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Medicin: RVU120

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

Andre navne:
  • SEL120
Medicin: Venetoclax

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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
(Part 1) recommended doses of RVU120 and venetoclax for further study
Tidsramme: approx. 12 months

Incidence and severity of toxicities and number of dose limiting toxicities per dose cohort
approx. 12 months
(Parts 2 & 3) CR/CRh rate (Complete Remission/Complete Remission with incomplete Hematologic Recovery)
Tidsramme: approx. 36 months

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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence and severity of adverse events (safety and tolerability)
Tidsramme: approx. 36 months

Number and grade of adverse events assessed by CTCAE v5.0
approx. 36 months
Duration of response
Tidsramme: approx. 36 months

Time from randomization to disease progression or death in patients who achieve CR/CRh
approx. 36 months
Post baseline transfusion independence rate
Tidsramme: approx. 36 months

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
Progression-free survival
Tidsramme: approx. 36 months

Time from randomization until first evidence of disease progression or death
approx. 36 months
Relapse-free survival
Tidsramme: approx. 36 months

Number of participants alive without relapse
approx. 36 months
Overall survival
Tidsramme: approx. 36 months

Time from randomization to death
approx. 36 months
Percentage of patients bridged to hematopoietic stem cell transplantation
Tidsramme: approx. 36 months

Number of hematopoietic stem cell transplantations following response
approx. 36 months
(Parts 2 & 3) Impact of treatment on HM-PRO (hematologic malignancy specific patient reported outcome measure)
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Ryvu Therapeutics SA

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

5. januar 2024

Primær færdiggørelse (Anslået)

1. august 2027

Studieafslutning (Anslået)

1. august 2027

Datoer for studieregistrering

Først indsendt

19. december 2023

Først indsendt, der opfyldte QC-kriterier

19. december 2023

Først opslået (Faktiske)

5. januar 2024

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • RIVER-81

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

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