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

Sponsor

Enliven Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05304377

Collaborator

(none)

120

Enrollment

Locations

Arms

54.3

Anticipated Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: ELVN-001	Phase 1

Detailed Description

This first-in-human trial with ELVN-001 is a dose escalation study whose primary purpose is to identify the recommended dose for expansion RDE of single agent ELVN-001 in chronic phase or accelerated phase CML with and 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 RDE safety profile, PK and preliminary evidence of anti-CML activity will be used to inform future development 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 tolerable or benefit from available TKIs.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 22, 2022

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: phase 1b expansion arm at recommended dose level 1 ELVN-001 administered orally once daily at RDE-1 in CML without T315I mutations	Drug: ELVN-001 orally once daily
Experimental: Phase 1b expansion arm at recommended dose level 2 ELVN-001 administered orally once daily at RDE-2 in CML without T315I mutations	Drug: ELVN-001 orally once daily
Experimental: Phase 1b expansion arm in T315I mutated CML ELVN-001 administered orally once daily at RDE-3	Drug: ELVN-001 orally once daily
Experimental: Phase 1a dose escalation in CML ELVN-001 administered orally once daily in 3+3 dose escalation	Drug: ELVN-001 orally once daily

Outcome Measures

Primary Outcome Measures

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 adverse events [up to 3 years]
Adverse events will be used to support that the dose(s) evaluated in expansion is 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

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 [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: frequency of complete cytogenetic remission (CCyR) [up to 3 years]
The proportion of patients who achieve CCyR by serum BCR-ABL1 transcript level who are not in CHR at baseline
Phase 1b: Rate of complete hematologic response (CHR) [up to 3 years]
The proportion of patients who achieve a CHR who are not in CHR at baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CML that has failed or the patient is intolerant to available therapies known to be active for treatment of their CML.
ECOG performance status of 0 to 2.
Adequate hematologic, hepatic and renal function.

Exclusion Criteria:

Treatment with anti-cancer or anti-CML therapy within 7 days or 5 half-lives, whichever is longer.
QTc >470 ms.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
2	Oregon Health & Science University-Knight Cardiovascular Institute	Portland	Oregon	United States	97239
3	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
4	Royal Adelaide Hospital	Adelaide		Australia	SA 5000
5	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux		France	33076
6	Centre Hospitalier de Versailles (CHV)	Le Chesnay		France	78157
7	CHRU de Lille - Hopital Calmette-Boulevard du Pr Leclercq CHRU Lille	Lille		France	59000
8	Centre Hospitalier Lyon Sud	Pierre Benite Cedex		France	69495
9	Uniklinik RWTH Aachen Medizinische Klinik III	Aachen		Germany	52074
10	Charite Campus Virchow	Berlin		Germany	13353
11	Klinikum der Goethe Universitat	Frankfurt		Germany	60596
12	Universitaetsklinikum Jena	Jena		Germany	07747
13	Medizinische Universitatsklinik Mannheim der Universitat Heidelberg	Mannheim		Germany	68167
14	Chonbuk National University Hospital	Jeonju	Jeollabuk-do	Korea, Republic of	54907
15	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of	42601
16	Uijeongbu Eulji Medical Center	Gyeonggi-do		Korea, Republic of	11749
17	Chonnam National University Hwasun Hospital	Hwasun		Korea, Republic of	58128
18	Samsung Medical Center	Seoul		Korea, Republic of	06351
19	Hospital Del Mar	Barcelona		Spain	08003
20	Hospital Universitario de Gran Canaria Dr. Negrin, Servicio Canario de Salud (SCS)	Las Palmas De Gran Canaria		Spain	35010
21	Hospital Universitario La Paz	Madrid		Spain	28046
22	Hospital Virgen de la Salud	Toledo		Spain	45007
23	Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)	Valencia		Spain	46026

Sponsors and Collaborators

Enliven Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Enliven Therapeutics

ClinicalTrials.gov Identifier:

NCT05304377

Other Study ID Numbers:

ELVN-001-101

First Posted:

Mar 31, 2022

Last Update Posted:

Aug 17, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

No Results Posted as of Aug 17, 2022