재발성/불응성 AML 치료를 위한 RVU120과 베네토클락스 병용의 안전성 및 유효성 (RIVER-81)
벤토클락스와 저메틸화제로 사전 치료에 실패한 급성 골수성 백혈병 참가자를 대상으로 베네토클락스와 병용한 RVU120의 안전성, 약동학, 약력학 및 임상 효능을 평가하기 위한 다기관, 공개 라벨, 용량 측정 임상 시험
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
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Head of Clinical Operations
- 전화번호: +48-12 -314-02-00
- 이메일: clinicaltrials@ryvu.com
연구 장소
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Barcelona, 스페인, 08003
- 모병
- Hospital Del Mar
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연락하다:
- Sara Garcia Avila, Dr
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수석 연구원:
- Sara Garcia Avila, Dr
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Barcelona, 스페인, 08908
- 아직 모집하지 않음
- Institut Catala D'oncologia
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연락하다:
- Montserrat Arnan Sangerman, Dr
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수석 연구원:
- Montserrat Arnan Sangerman, Dr
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Barcelona, 스페인, 08041
- 모병
- Hospital De La Santa Creu I Sant Pau
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연락하다:
- Guadalupe Oñate, Dr
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수석 연구원:
- Guadalupe Oñate, Dr
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Cáceres, 스페인, 10002
- 모병
- Hospital San Pedro De Alcantara
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연락하다:
- Juan Miguel Bergua Burgués, Dr
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수석 연구원:
- Juan Miguel Bergua Burgués, Dr
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Madrid, 스페인, 28046
- 모병
- Hospital Universitario La Paz
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연락하다:
- Irene Sanchez Vandillo, Dr
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수석 연구원:
- Irene Sanchez Vandillo, Dr
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Madrid, 스페인, 28033
- 모병
- MD Anderson Cancer Center
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연락하다:
- Adolfo De La Fuente, Dr
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수석 연구원:
- Adolfo De La Fuente, Dr
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Málaga, 스페인, 29010
- 모병
- Hospital Universitario Regional De Malaga
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연락하다:
- Alejandro Luis Contento Gonzalo, Dr
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수석 연구원:
- Alejandro Luis Contento Gonzalo, Dr
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Pamplona, 스페인, 31008
- 모병
- Clinica Universidad De Navarra
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연락하다:
- Ana Alfonso Pierola, Dr
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수석 연구원:
- Ana Alfonso Pierola, Dr
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Seville, 스페인, 41013
- 모병
- University Hospital Virgen Del Rocio S.L.
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연락하다:
- Jose Antonio Perez Simón, Dr
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수석 연구원:
- Jose Antonio Perez Simón, Dr
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Valencia, 스페인, 46026
- 모병
- Hospital Universitario Y Politecnico La Fe
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연락하다:
- Pau Montesinos Fernandez, Dr
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수석 연구원:
- Pau Montesinos Fernandez, Dr
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Ancona, 이탈리아, 60126
- 모병
- Azienda Ospedaliero Universitaria Delle Marche
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연락하다:
- Debora Capelli, Dr
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수석 연구원:
- Debora Capelli, Dr
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Bologna, 이탈리아, 40138
- 모병
- Univerisity of Bologna Policlinico Sant'Orsola
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연락하다:
- Cristina Papayannidis, Prof.
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수석 연구원:
- Cristina Papayannidis, Prof.
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Brescia, 이탈리아, 25123
- 모병
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
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연락하다:
- Erika Borlenghi, Dr
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수석 연구원:
- Erika Borlenghi, Dr
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Lecce, 이탈리아, 73100
- 모병
- Ospedale Vito Fazzi Lecce
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연락하다:
- Nicola Di Renzo, Dr
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수석 연구원:
- Nicola Di Renzo, Dr
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Ravenna, 이탈리아
- 모병
- AUSL Romagna - Ospedale S.M. Delle Croci
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수석 연구원:
- Giovanni Marconi, Prof.
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Roma, 이탈리아, 00133
- 모병
- Azienda Ospedaliera Policlinico Universitario Tor Vergata
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연락하다:
- Adriano Venditti, Prof.
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수석 연구원:
- Adriano Venditti, Prof.
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Rozzano, 이탈리아
- 모병
- Istituto Clinico Humanitas
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수석 연구원:
- Matteo Della Porta, Prof.
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Turin, 이탈리아, 10126
- 모병
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
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연락하다:
- Ernesta Audisio, Dr
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수석 연구원:
- Ernesta Audisio, Dr
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Forlì-Cesena
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Meldola, Forlì-Cesena, 이탈리아, 47014
- 모병
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
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연락하다:
- Maria Giannini, Dr
- 전화번호: +39 0543 739100
- 이메일: info@irst.emr.it
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수석 연구원:
- Maria Giannini, Dr
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Biała Podlaska, 폴란드, 21-500
- 종료됨
- Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
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Gdansk, 폴란드, 80-214
- 모병
- Uniwersyteckie Centrum Kliniczne
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수석 연구원:
- Witold Prejzner, Dr
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연락하다:
- Witold Prejzner, Dr
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Katowice, 폴란드
- 모병
- PRATIA Onkologia Katowice
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수석 연구원:
- Sebastian Grosicki, Prof.
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Torun, 폴란드, 87-100
- 종료됨
- Wojewodzki Szpital Zespolony Im.L.Rydygiera w Toruniu
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Warsaw, 폴란드, 02-776
- 모병
- Instytut Hematologii i Transfuzjologii
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연락하다:
- Ewa Lech-Marańda, Prof.
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수석 연구원:
- Ewa Lech-Marańda, Prof.
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Warsaw, 폴란드, 04-141
- 종료됨
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
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Wałbrzych, 폴란드, 58-309
- 모병
- Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
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연락하다:
- Aleksandra Butrym, Prof.
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수석 연구원:
- Aleksandra Butrym, Prof.
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Wroclaw, 폴란드, 53-439
- 모병
- Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii
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연락하다:
- Jarosław Dybko, Dr
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수석 연구원:
- Jarosław Dybko, Dr
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Zielona Góra, 폴란드, 65-046
- 종료됨
- 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, 폴란드, 02-172
- 모병
- MTZ Clinical Research
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연락하다:
- Krzysztof Mądry
- 전화번호: +48 22 572 59 59
- 이메일: info@pratia.com
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수석 연구원:
- Krzysztof Mądry
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Grenoble, 프랑스, 38043
- 모병
- Centre Hospitalier Universitaire Grenoble Alpes
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연락하다:
- Claude-Eric Bulabois, Dr
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수석 연구원:
- Claude-Eric Bulabois, Dr
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Le Mans, 프랑스, 72037
- 모병
- Centre Hospitalier Le Mans
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수석 연구원:
- Kamel Laribi, Dr
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연락하다:
- Kamel Laribi, Dr
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Lille, 프랑스, 59000
- 모병
- Centre Hospitalier Universitaire De Lille
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연락하다:
- Laure Goursaud, Dr
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수석 연구원:
- Laure Goursaud, Dr
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Marseille, 프랑스, 13009
- 모병
- Institut Paoli-Calmettes
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연락하다:
- Sylvian Garciaz, Dr
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수석 연구원:
- Sylvian Garciaz, Dr
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Nice, 프랑스, 06200
- 모병
- Centre Hospitalier Universitaire De Nice
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연락하다:
- Thomas Cluzeau, Dr
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수석 연구원:
- Thomas Cluzeau, Dr
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Nîmes, 프랑스, 30900
- 모병
- Centre Hospitalier Universitaire De Nimes
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수석 연구원:
- Stefan Wickenhauser, Dr
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연락하다:
- Stefan Wickenhauser, Dr
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Paris, 프랑스, 75010
- 모병
- Assistance Publique Hopitaux De Paris
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연락하다:
- Pierre Fenaux, Dr
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수석 연구원:
- Pierre Fenaux, Dr
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Rouen, 프랑스, 76000
- 모병
- Centre Henri Becquerel
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연락하다:
- Emilie Lemasle-Hue, Dr
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수석 연구원:
- Emilie Lemasle-Hue, Dr
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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
다른 이름들:
Venetoclax specifically binds to BCL-2, displacing proapoptotic proteins and triggering events that lead to apoptosis |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
(Part 1) recommended doses of RVU120 and venetoclax for further study
기간: 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)
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Incidence and severity of adverse events (safety and tolerability)
기간: approx. 36 months
|
Number and grade of adverse events assessed by CTCAE v5.0 |
approx. 36 months
|
|
Duration of response
기간: 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
기간: 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
기간: approx. 36 months
|
Time from randomization until first evidence of disease progression or death |
approx. 36 months
|
|
Relapse-free survival
기간: approx. 36 months
|
Number of participants alive without relapse |
approx. 36 months
|
|
Overall survival
기간: approx. 36 months
|
Time from randomization to death |
approx. 36 months
|
|
Percentage of patients bridged to hematopoietic stem cell transplantation
기간: 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)
기간: 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
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- RIVER-81
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .