Chronic Phase CML, CML (Chronic Myelogenous Leukemia)
Conditions
Keywords
CML, Tyrosine Kinase Inhibitor, T315I, T315I Mutant, BCR-ABL
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 Japanese patients with chronic phase chronic myeloid leukemia with and without T315I mutations in patients who has failed, or the patient is intolerant to, or not a candidate for, at least 2 prior 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 have failed, or are intolerant to, or not a candidate for, at least 2 prior TKIs.
Interventions
DRUGELVN-001
Orally once or twice daily
Sponsors
Enliven Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* BCR::ABL1 positive CP-CML that has failed, or the patient is intolerant to, or not a candidate for, at least 2 prior TKIs. * ECOG performance status of 0 to 2. * The patient was born in Japan and both parents and grandparents are Japanese. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: 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 exploration is tolerable |
| Part 1: Incidence of dose limiting toxicities | 28 days | DLTs will be used to support that the recommended doses for expansion are \</= MTD |
| Part 1: 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 |
| Part 1: 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 |
| Part 1: 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 |
| Part 2: Incidence of adverse events | Up to 3 years | Adverse events will be used to support that the dose(s) evaluated in exploration is tolerable |
| Part 2: 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 exploration is tolerable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve | 6 months | PK parameter based on measurement of drug concentration in blood over time |
| Maximum concentration | 6 months | PK parameter based on measurement of drug concentration in blood |
| Time of maximum concentration | 6 months | PK parameter which is the time at which the highest concentration of drug in the blood is measured |
| 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. |
| Molecular response (MR) | Up to 3 years | Measured by quantitative polymerase chain reaction of BCR-ABL transcript levels |
| 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 |
| Complete Hematologic Response (CHR) | Up to 3 years | The proportion of patients who achieve a CHR who are not in CHR at baseline |
Countries
Japan
Contacts
Primary ContactYuzo Tomonaga
Outcome results
None listed