Clinical trial NCT05304377: A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia
Official title: A Phase 1a/1b Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia
Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
Cml
Keywords: CML
Tyrosine kinase inhibitor
T315I
T315I mutant
BCR-ABL
ENABLE
active site inhibitor of BCR-ABL
Lead sponsor: Enliven Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* BCR-ABL1 positive CML in chronic phase, with or without T315I mutation.
* The patient has failed, is intolerant to, or not a candidate for, available therapies known to be active for treatment of their CML.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Phase 1a: Incidence of dose limiting toxicities
timeFrame: 28 days
measure: Phase 1a: Incidence of adverse events (AEs)
timeFrame: up to 28 days
measure: Phase 1a: Incidence of clinically significant laboratory abnormalities
timeFrame: up to 28 days
measure: Phase 1a: Incidence of clinically significant ECG abnormalities
timeFrame: up to 28 days
measure: Phase 1b: Incidence of adverse events
timeFrame: up to 3 years
measure: Phase 1b: Incidence of clinically significant laboratory abnormalities
timeFrame: up to 3 years
measure: Phase 1b: Incidence of clinically significant ECG abnormalities
timeFrame: up to 3 years
Secondary outcomes:
measure: Phase 1a and 1b: area under the curve
timeFrame: 6 months
measure: Phase 1a and 1b: maximum concentration
timeFrame: 6 months
measure: Phase 1a and 1b: time of maximum concentration
timeFrame: 6 months
measure: Phase 1a and 1b: minimum concentration
timeFrame: 6 months
measure: Phase 1a and 1b: Molecular response (MR)
timeFrame: up to 3 years
measure: Phase 1b: Duration of Molecular Response
timeFrame: up to 3 years
measure: Phase 1b: Complete Hematologic Response (CHR)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University-Knight Cardiovascular Institute
state: Oregon
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Gent
country: Belgium
facility: UZ Gent
city: Toronto
country: Canada
facility: University Health Network (UHN) - Princess Margaret Cancer Centre
state: Ontario
city: Amiens
country: France
facility: CHU Amiens Picardie Site Sud
city: Bordeaux
country: France
facility: Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles (CHV)
city: Lille
country: France
facility: CHRU de Lille - Hopital Calmette-Boulevard du Pr Leclercq CHRU Lille
city: Limoges
country: France
facility: Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen Medizinische
city: Berlin
country: Germany
facility: Charite Campus Virchow
city: Frankfurt
country: Germany
facility: Klinikum der Goethe Universitat
city: Homburg
country: Germany
facility: Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Mannheim
country: Germany
facility: Medizinische Universitatsklinik Mannheim der Universitat Heidelberg
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: The Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Delle Marche
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
state: Jeollabuk-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Uijeongbu Eulji Medical Center
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Nowy Sącz
country: Poland
facility: Szpital Specjalistycnzy im. Jedrzeja Sniadeckiego w Nowym Saczu
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Torun
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin, Servicio Canario e Salud (SCS)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Toledo
country: Spain
facility: Complejo Hospitalario de Toledo - Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre, Gartnavel General Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital Imperial College Healthcare NHS Trust
Study officials:
References: