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

Chronic Myeloid Leukemia Clinical Trial

— CML  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05304377
• Other study ID #: ELVN-001-101
• Status: Recruiting
• Phase: Phase 1
• Start date: May 22, 2022
• Est. completion date: December 2026

Study information

• Verified date: June 2024
• Source: Enliven Therapeutics
• Contact: Study Contact
• Phone: 707-799-3272
• Email: ELVN-001-101[@]enliventherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• ELVN-001
orally once or twice daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Canada	University Health Network (UHN) - Princess Margaret Cancer Centre	Toronto	Ontario
France	CHU Amiens Picardie Site Sud	Amiens
France	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	Centre Hospitalier de Versailles (CHV)	Le Chesnay
France	CHRU de Lille - Hopital Calmette-Boulevard du Pr Leclercq CHRU Lille	Lille
France	Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren	Limoges
France	Centre Leon Berard	Lyon
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
Germany	Uniklinik RWTH Aachen Medizinische Klinik III	Aachen
Germany	Charite Campus Virchow	Berlin
Germany	Klinikum der Goethe Universitat	Frankfurt
Germany	Universitaetsklinikum Jena	Jena
Germany	Medizinische Universitatsklinik Mannheim der Universitat Heidelberg	Mannheim
Germany	Universitaetsmedizin Rostock	Rostock
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Uijeongbu Eulji Medical Center	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Chonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario de Gran Canaria Dr. Negrin, Servicio Canario e Salud (SCS)	Las Palmas De Gran Canaria
Spain	Hospital Universitario La Paz	Madrid
Spain	Complejo Hospitalario de Toledo - Hospital Virgen de la Salud	Toledo
Spain	Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)	Valencia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health & Science University-Knight Cardiovascular Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Enliven Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Incidence of dose limiting toxicities	DLTs will be used to support that the recommended doses for expansion are	28 days
Primary	Phase 1a: Incidence of adverse events (AEs)	Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable	up to 28 days
Primary	Phase 1a: Incidence of clinically significant laboratory abnormalities	Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable	up to 28 days
Primary	Phase 1a: Incidence of clinically significant ECG abnormalities	Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable	up to 28 days
Primary	Phase 1b: Incidence of adverse events	Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable	up to 3 years
Primary	Phase 1b: Incidence of clinically significant laboratory abnormalities	Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable	up to 3 years
Primary	Phase 1b: Incidence of clinically significant ECG abnormalities	Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable	up to 3 years
Secondary	Phase 1a and 1b: area under the curve	PK parameter based on measurement of drug concentration in blood over time	6 months
Secondary	Phase 1a and 1b: maximum concentration	PK parameter based on measurement of drug concentration in blood	6 months
Secondary	Phase 1a and 1b: time of maximum concentration	PK parameter which is the time at which the highest concentration of drug in the blood is measured	6 months
Secondary	Phase 1a and 1b: minimum concentration	PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.	6 months
Secondary	Phase 1a and 1b: Molecular response (MR)	measured by quantitative polymerase chain reaction of BCR-ABL transcript levels	up to 3 years
Secondary	Phase 1b: Duration of Molecular Response	Time from first molecular response (as measured by quantitative polymerase chain reaction of BCR-ABL transcript levels) to loss of response or discontinuation of study drug	up to 3 years
Secondary	Phase 1b: Complete Hematologic Response (CHR)	The proportion of patients who achieve a CHR who are not in CHR at baseline	up to 3 years