A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia
- Conditions
- Chronic Myeloid LeukemiaChronic Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveCml
- Interventions
- Registration Number
- NCT05304377
- Lead Sponsor
- Enliven Therapeutics
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a Dose Escalation ELVN-001 ELVN-001 administered in 3+3 dose escalation Phase 1b Dose Expansion at recommended dose level 1 ELVN-001 ELVN-001 administered at the recommended dose in CML without T315I mutations Phase 1b Dose Expansion at recommended dose level 2 ELVN-001 ELVN-001 administered at a different recommended dose in CML without T315I mutations Phase 1b expansion arm in T315I mutated CML ELVN-001 ELVN-001 administered at the recommended dose for CML with T315I mutation
- Primary Outcome Measures
Name Time Method Phase 1b: Incidence of adverse events up to 3 years Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable
Phase 1a: Incidence of dose limiting toxicities 28 days DLTs will be used to support that the recommended doses for expansion are \</= MTD
Phase 1a: Incidence of adverse events (AEs) up to 28 days Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1a: Incidence of clinically significant laboratory abnormalities up to 28 days Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1a: Incidence of clinically significant ECG abnormalities up to 28 days Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1b: Incidence of clinically significant laboratory abnormalities up to 3 years Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable
Phase 1b: Incidence of clinically significant ECG abnormalities up to 3 years Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable
- Secondary Outcome Measures
Name Time Method Phase 1a and 1b: area under the curve 6 months PK parameter based on measurement of drug concentration in blood over time
Phase 1a and 1b: maximum concentration 6 months PK parameter based on measurement of drug concentration in blood
Phase 1a and 1b: time of maximum concentration 6 months PK parameter which is the time at which the highest concentration of drug in the blood is measured
Phase 1a and 1b: minimum concentration 6 months PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.
Phase 1a and 1b: Molecular response (MR) up to 3 years measured by quantitative polymerase chain reaction of BCR-ABL transcript levels
Phase 1b: Duration of Molecular Response up to 3 years 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
Phase 1b: Complete Hematologic Response (CHR) up to 3 years The proportion of patients who achieve a CHR who are not in CHR at baseline
Trial Locations
- Locations (34)
The Galilee Medical Center
🇮🇱Nahariya, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Oregon Health & Science University-Knight Cardiovascular Institute
🇺🇸Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
University Health Network (UHN) - Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
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, France
Uniklinik RWTH Aachen Medizinische Klinik III
🇩🇪Aachen, Germany
Charite Campus Virchow
🇩🇪Berlin, Germany
Klinikum der Goethe Universitat
🇩🇪Frankfurt, Germany
Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
🇩🇪Homburg, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Medizinische Universitatsklinik Mannheim der Universitat Heidelberg
🇩🇪Mannheim, Germany
Universitaetsmedizin Rostock
🇩🇪Rostock, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Chonbuk National University Hospital
🇰🇷Jeonju, Jeollabuk-do, 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
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
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, Spain
Beatson West of Scotland Cancer Centre, Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Hammersmith Hospital Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom