Chronic Myeloid Leukemia, Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive, Cml
Conditions
Keywords
CML, Tyrosine kinase inhibitor, T315I, T315I mutant, BCR-ABL, ENABLE, active site inhibitor of 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 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.
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTStudy Contact
Outcome results
None listed