A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia

Официальное название

A Phase 1a/1b Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia

Обзор

The purpose of this study is to evaluate the safety, tolerability and determine the recommended dose for further clinical evaluation of ELVN-001 in patients with chronic myeloid leukemia with and without T315I mutations in patients who are relapsed, refractory or intolerant to TKIs.

Подробное описание

This first-in-human trial with ELVN-001 is a dose escalation study with the primary purpose to identify the recommended dose(s) for expansion (RDEs) of single agent ELVN-001 in chronic phase CML with or without T315I mutations. The safety, tolerability and pharmacokinetic profile of ELVN-001 will be assessed together with an evaluation of changes in BCR-ABL1 transcript. An understanding of the safety profile, PK and preliminary evidence of anti-CML activity will be used to inform future development of ELVN-001 in adults with CML. By virtue of its predicted pharmacological profile ELVN-001 has the potential to be tolerable and achieve a deep molecular response in patients with CML with or without T315I mutations who do not tolerate or benefit from available TKIs.

Вмешательства

• Препарат ELVN-001
  orally once or twice daily

Первичные конечные точки

• Phase 1a: Incidence of dose limiting toxicities [Срок оценки: 28 days]
• Phase 1a: Incidence of adverse events (AEs) [Срок оценки: up to 28 days]
• Phase 1a: Incidence of clinically significant laboratory abnormalities [Срок оценки: up to 28 days]
• Phase 1a: Incidence of clinically significant ECG abnormalities [Срок оценки: up to 28 days]
• Phase 1b: Incidence of adverse events [Срок оценки: up to 3 years]
• Phase 1b: Incidence of clinically significant laboratory abnormalities [Срок оценки: up to 3 years]
• Phase 1b: Incidence of clinically significant ECG abnormalities [Срок оценки: up to 3 years]

Вторичные конечные точки (7)

• Phase 1a and 1b: area under the curve [Срок оценки: 6 months]
• Phase 1a and 1b: maximum concentration [Срок оценки: 6 months]
• Phase 1a and 1b: time of maximum concentration [Срок оценки: 6 months]
• Phase 1a and 1b: minimum concentration [Срок оценки: 6 months]
• Phase 1a and 1b: Molecular response (MR) [Срок оценки: up to 3 years]
• Phase 1b: Duration of Molecular Response [Срок оценки: up to 3 years]
• Phase 1b: Complete Hematologic Response (CHR) [Срок оценки: up to 3 years]

Критерии участия

Критерии включения

• BCR-ABL1 positive CML in chronic phase, with or without T315I mutation.
• US: The patient has failed or is intolerant to at least one prior second-generation tyrosine kinase inhibitor (TKI) or asciminib. Rest of World: The patient has failed, is intolerant to, or not a candidate for, available therapies known to be active for treatment of their CML (country-specific criteria may vary).
• ECOG performance status of 0 to 2.
• Adequate hematologic, hepatic and renal function.
• Prior bone marrow transplant allowed if ≥ 6 months prior to the first dose of ELVN-001.

Критерии исключения

• Treatment with anti-cancer or anti-CML therapy within 7 days or 5 half-lives, whichever is longer.
• History of acute tyrosine kinase inhibitor (TKI)-related pancreatitis within 6 months of study entry. Active chronic pancreatitis, or pancreatic disease due to any cause.
• QTc >470 ms.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 7 центров

• Uniklinik RWTH Aachen Medizinische — Aachen
• Charite Campus Virchow — Berlin
• Klinikum der Goethe Universitat — Frankfurt
• Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarl — Homburg
• Universitaetsklinikum Jena — Jena
• Medizinische Universitatsklinik Mannheim der Universitat Heidelberg — Mannheim
• Universitaetsmedizin Rostock — Rostock

Франция · 6 центров

• CHU Amiens Picardie Site Sud — Amiens
• Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest — Bordeaux
• CHRU de Lille - Hopital Calmette-Boulevard du Pr Leclercq CHRU Lille — Lille
• Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren — Limoges
• Centre Leon Berard — Lyon
• Centre Hospitalier Lyon Sud — Pierre-Bénite

South Korea · 5 центров

• Chonbuk National University Hospital — Jeonju
• Keimyung University Dongsan Hospital — Daegu
• Uijeongbu Eulji Medical Center — Gyeonggi-do
• Chonnam National University Hwasun Hospital — Hwasun
• Samsung Medical Center — Seoul

Испания · 5 центров

• Hospital Del Mar — Barcelona
• Hospital Universitario de Gran Canaria Dr. Negrin, Servicio Canario e Salud (SCS) — Las Palmas de Gran Canaria
• Hospital Universitario La Paz — Madrid
• Complejo Hospitalario de Toledo - Hospital Virgen de la Salud — Toledo
• Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital L — Valencia

США · 4 центра

• Memorial Sloan Kettering Cancer Center — New York
• Montefiore Medical Center — The Bronx
• Oregon Health & Science University-Knight Cardiovascular Institute — Portland
• The University of Texas MD Anderson Cancer Center — Houston

Бельгия · 3 центра

• UZ Gent — Ghent
• UZ Leuven — Leuven
• CHU Liege — Liège

Израиль · 3 центра

• Hadassah Medical Center — Jerusalem
• The Galilee Medical Center — Nahariya
• Rabin Medical Center — Petah Tikva

Польша · 3 центра

• Szpital Specjalistycnzy im. Jedrzeja Sniadeckiego w Nowym Saczu — Nowy Sącz
• MICS Centrum Medyczne Torun — Torun
• Instytut Hematologii I Transfuzjologii — Warsaw

Великобритания · 3 центра

• Beatson West of Scotland Cancer Centre, Gartnavel General Hospital — Glasgow
• Hammersmith Hospital Imperial College Healthcare NHS Trust — London
• The Christie NHS Foundation Trust — Manchester

Венгрия · 2 центра

• Semmelweis Egyetem, Belgyogyaszati es Onkologiai Klinika — Budapest
• Pecsi Tudomanyegyetem Klinikai Kozpont (University of Pecs, Clinical Centre) — Pécs

Австралия · 1 центр

• Royal Adelaide Hospital — Adelaide

Канада · 1 центр

• University Health Network (UHN) - Princess Margaret Cancer Centre — Toronto

Италия · 1 центр

• Azienda Ospedaliero Universitaria Delle Marche — Ancona

Нидерланды · 1 центр

• Radboud University Medical Center — Nijmegen

Идентификаторы

NCT: NCT05304377 · ELVN-001-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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