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Sikkerhet og effekt av RVU120 kombinert med Venetoclax for behandling av residiverende/refraktær AML (RIVER-81)

15. september 2026 oppdatert av: Ryvu Therapeutics SA

En multisenter, åpen, dosefinnende klinisk studie for å vurdere sikkerheten, farmakokinetikken, farmakodynamikken og den kliniske effekten av RVU120 i kombinasjon med Venetoclax hos deltakere med akutt myeloid leukemi som mislyktes i tidligere behandling med Ventoclax og et hypometylerende 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

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Antatt)

98

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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
Legemiddel: RVU120

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

Andre navn:
  • SEL120
Legemiddel: Venetoclax

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

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Ryvu Therapeutics SA

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

5. januar 2024

Primær fullføring (Antatt)

1. august 2027

Studiet fullført (Antatt)

1. august 2027

Datoer for studieregistrering

Først innsendt

19. desember 2023

Først innsendt som oppfylte QC-kriteriene

19. desember 2023

Først lagt ut (Faktiske)

5. januar 2024

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

15. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • RIVER-81

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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