Chronic Myeloid Leukemia (CML), Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive, Chronic Phase Chronic Myeloid Leukemia, BCR::ABL1 Positive CML
Conditions
Keywords
Chronic Myeloid Leukemia, CML, ELVN-001, Philadelphia chromosome, Tyrosine kinase inhibitor, TKI, TKIs, ENABLE-2, Bosutinib, Dasatinib, Nilotinib, Molecular Response, BCR::ABL, Active site inhibitor of BCR::ABL
Brief summary
The study is designed to compare the efficacy of ELVN-001 versus Investigator-selected tyrosine kinase inhibitor (TKI) for adults with previously treated chronic myeloid leukemia in the chronic phase (CP-CML). The Investigator-selected TKI will be one of the following standard of care therapies: Dasatinib, Nilotinib, or Bosutinib.
Detailed description
This is a multicenter, open-label, randomized study of ELVN-001 versus Investigator-selected TKI (Dasatinib, Nilotinib, or Bosutinib) in adult participants with CP-CML previously treated with one or more TKIs. Participants will be randomized to receive either ELVN-001 or their investigator's choice of one of the comparator TKIs (Dasatinib, Nilotinib, or Bosutinib). Treatment will continue until one of the protocol defined treatment discontinuation criteria are met. Participants will then enter a long-term follow-up period for survivorship and updates on disease status.
Sponsors
Enliven Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female at least 18 years of age * Diagnosis of chronic myeloid leukemia in chronic phase (CP-CML) * Prior treatment with 1 or more BCR::ABL1 TKI(s) * Failure or intolerance on the immediate prior TKI * Adequate end organ function as measured by blood tests
Exclusion criteria
* Known T315I mutation * Known second chronic phase of CML after previous progression to accelerated or blast phase * Any serious or uncontrolled medical disorder * QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec * Previous treatment with a hematopoietic stem-cell transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Molecular Response (MMR) Rate at Week 24 - ELVN-001 versus Investigator-selected TKI | 24 weeks | Molecular response is assessed using BCR::ABL1 transcript levels measured by quantitative polymerase chain reaction (qPCR). MMR is defined as a ratio BCR::ABL/ABL1 ≤ 0.1% on the International Scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Molecular Response (MMR) Rate at Week 96 - ELVN-001 versus Investigator-selected TKI | 96 weeks | Molecular response is assessed using BCR::ABL1 transcript levels measured by quantitative polymerase chain reaction (qPCR). MMR is defined as a ratio BCR::ABL/ABL1 ≤ 0.1% on the International Scale. |
| Change in overall scores, individual scales, and health status based on participant reporting - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Validated questionnaires will be used to assess disease-related symptoms, functioning, and tolerability. |
| Major Molecular Response (MMR) at all scheduled collection time points - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Molecular response is assessed using BCR::ABL1 transcript levels measured by quantitative polymerase chain reaction (qPCR). MMR is defined as a ratio BCR::ABL/ABL1 ≤ 0.1% on the International Scale |
| Major Molecular Response (MMR) by all scheduled collection time points - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Molecular response is assessed using BCR::ABL1 transcript levels measured by quantitative polymerase chain reaction (qPCR). MMR is defined as a ratio BCR::ABL/ABL1 ≤ 0.1% on the International Scale |
| Time to Major Molecular Response (MMR) - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | The time to MMR is defined as the time from the date of randomization to the date of the first documented occurrence of MMR |
| Duration of Major Molecular Response (MMR) - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Duration of MMR is defined as the time between the date of the first achievement of MMR and the earliest date of loss of MMR or CML-related death |
| BCR::ABL1 ratio ≤ 1% at and by all scheduled data collection time points - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | BCR::ABL1 transcript levels are measured by quantitative polymerase chain reaction (qPCR). The ratio is calculated for BCR::ABL/ABL1 based on the International Scale |
| Time to treatment failure - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Time to treatment failure is defined as the time from randomization to the first date of any of the following events: treatment failure as defined per protocol |
| Progression-free survival - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Progression-free survival is defined as the time from randomization to the earliest occurrence of progression or death from any cause |
| Overall survival (OS) - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | OS is defined as the time from randomization to death from any cause |
| MR4 and MR4.5 at and by all scheduled data collection time points - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Molecular response is assessed using BCR::ABL1 transcript levels measured by quantitative polymerase chain reaction (qPCR). MR4 is defined as a ratio BCR::ABL/ABL1 ≤ 0.01% on the International Scale and MR4.5 is defined as a ratio BCR::ABL/ABL1 ≤ 0.0032% on the International Scale |
| Time to treatment discontinuation due to adverse event (AE) - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | This is defined as the time from randomization to discontinuation of study treatment due to an adverse event |
| Characterization of adverse events (AE) and clinically relevant findings, including laboratory abnormalities, electrocardiogram (ECG) changes, and other safety data - ELVN-001 versus Investigator-selected TKI | planned total follow-up duration of 5 years | Characteristics of AEs will be evaluated to assess safety and tolerability profiles |
| Plasma concentrations of ELVN-001 in participants treated with ELVN-001 will be assessed at all scheduled collection timepoints | planned total follow-up duration of 5 years | Relevant pharmacokinetic parameters will be evaluated |
Contacts
CONTACTEnliven Medical Information
Outcome results
None listed