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.
Brief Title
A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
707-799-3272
Central Contact Email
ELVN-001-101@enliventherapeutics.com
Completion Date
Completion Date Type
Estimated
Conditions
Chronic Myeloid Leukemia
Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
Cml
Eligibility Criteria
Inclusion Criteria:
* 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.
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.
* 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.
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.
Inclusion Criteria
Inclusion Criteria:
* 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.
* 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.
Gender
All
Gender Based
false
Keywords
CML
Tyrosine kinase inhibitor
T315I
T315I mutant
BCR-ABL
ENABLE
active site inhibitor of BCR-ABL
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05304377
Org Class
Industry
Org Full Name
Enliven Therapeutics
Org Study Id
ELVN-001-101
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1a/1b Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia
Primary Outcomes
Outcome Description
DLTs will be used to support that the recommended doses for expansion are \</= MTD
Outcome Measure
Phase 1a: Incidence of dose limiting toxicities
Outcome Time Frame
28 days
Outcome Description
Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable
Outcome Measure
Phase 1a: Incidence of adverse events (AEs)
Outcome Time Frame
up to 28 days
Outcome Description
Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Outcome Measure
Phase 1a: Incidence of clinically significant laboratory abnormalities
Outcome Time Frame
up to 28 days
Outcome Description
Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Outcome Measure
Phase 1a: Incidence of clinically significant ECG abnormalities
Outcome Time Frame
up to 28 days
Outcome Description
Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable
Outcome Measure
Phase 1b: Incidence of adverse events
Outcome Time Frame
up to 3 years
Outcome Description
Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable
Outcome Measure
Phase 1b: Incidence of clinically significant laboratory abnormalities
Outcome Time Frame
up to 3 years
Outcome Description
Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable
Outcome Measure
Phase 1b: Incidence of clinically significant ECG abnormalities
Outcome Time Frame
up to 3 years
Secondary Outcomes
Outcome Description
PK parameter based on measurement of drug concentration in blood over time
Outcome Time Frame
6 months
Outcome Measure
Phase 1a and 1b: area under the curve
Outcome Description
PK parameter based on measurement of drug concentration in blood
Outcome Time Frame
6 months
Outcome Measure
Phase 1a and 1b: maximum concentration
Outcome Description
PK parameter which is the time at which the highest concentration of drug in the blood is measured
Outcome Time Frame
6 months
Outcome Measure
Phase 1a and 1b: time of maximum concentration
Outcome Description
PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.
Outcome Time Frame
6 months
Outcome Measure
Phase 1a and 1b: minimum concentration
Outcome Description
measured by quantitative polymerase chain reaction of BCR-ABL transcript levels
Outcome Time Frame
up to 3 years
Outcome Measure
Phase 1a and 1b: Molecular response (MR)
Outcome Description
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
Outcome Time Frame
up to 3 years
Outcome Measure
Phase 1b: Duration of Molecular Response
Outcome Description
The proportion of patients who achieve a CHR who are not in CHR at baseline
Outcome Time Frame
up to 3 years
Outcome Measure
Phase 1b: Complete Hematologic Response (CHR)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Levitz
Investigator Email
dlevitz@montefiore.org
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood & Bone Marrow Cancers --- NEOPLASMS BY HISTOLOGIC TYPE
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE
LEUKEMIA, MYELOID, CHRONIC-PHASE
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
MYELOPROLIFERATIVE DISORDERS
BONE MARROW DISEASES
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS