A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT05304377
Intervention or treatment
DRUG: ELVN-001
Conditions
- Chronic Myeloid Leukemia
- Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
- Cml
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Research sites nearby
Closest Location:
Royal Adelaide Hospital
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Royal Adelaide Hospital
Adelaide, Australia
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Who is running the clinical trial?
Enliven Therapeutics
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Phase 1a Dose Escalation
| Drug: ELVN-001 |
EXPERIMENTAL: Phase 1b Dose Expansion (non-T315I)
| Drug: ELVN-001 |
EXPERIMENTAL: Phase 1b expansion (T315I)
| Drug: ELVN-001 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a: Incidence of dose limiting toxicities | DLTs will be used to support that the recommended doses for expansion are \</= MTD | 28 days |
| Phase 1a: Incidence of adverse events (AEs) | Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable | up to 28 days |
| Phase 1a: Incidence of clinically significant laboratory abnormalities | Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable | up to 28 days |
| Phase 1a: Incidence of clinically significant ECG abnormalities | Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable | up to 28 days |
| Phase 1b: Incidence of adverse events | Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable | up to 3 years |
| Phase 1b: Incidence of clinically significant laboratory abnormalities | Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable | up to 3 years |
| Phase 1b: Incidence of clinically significant ECG abnormalities | Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable | up to 3 years |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a and 1b: area under the curve | PK parameter based on measurement of drug concentration in blood over time | 6 months |
| Phase 1a and 1b: maximum concentration | PK parameter based on measurement of drug concentration in blood | 6 months |
| Phase 1a and 1b: time of maximum concentration | PK parameter which is the time at which the highest concentration of drug in the blood is measured | 6 months |
| Phase 1a and 1b: minimum concentration | PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved. | 6 months |
| Phase 1a and 1b: Molecular response (MR) | measured by quantitative polymerase chain reaction of BCR-ABL transcript levels | up to 3 years |
| Phase 1b: Duration of Molecular Response | 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 | up to 3 years |
| Phase 1b: Complete Hematologic Response (CHR) | The proportion of patients who achieve a CHR who are not in CHR at baseline | up to 3 years |
References
Clinical Trials Gov: A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid LeukemiaOther trials to consider
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