Chronic Myeloid Leukemia, CML, CML, Chronic Phase
Conditions
Brief summary
Study comparing efficacy and safety of olverembatinib (investigational arm) vs. bosutinib (control arm) in patients with CML-CP (Part A). Study will also evaluate efficacy and safety of olverembatinib (single-arm) in CML-CP patients with T315I mutation (Part B). Patients who meet ELN 2025 failure criteria while receiving bosutinib in Part A may be able to receive olverembatinib in crossover follow-on study.
Interventions
DRUGolverembatinib
olverembatinib QOD
DRUGBosutinib
Bosutnib QD
Sponsors
Ascentage Pharma Group Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A (285 patients): Randomization to olverembatinib or bosutinib at 2:1 ratio. Part B in patients with T315I mutation (48 patients): Single-arm part; all enrolled patients receive olverembatinib.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients eligible for inclusion in this study must meet all of the following criteria: 1. Age ≥ 18 years old 2. Diagnosis of CML-CP 3. Part A: Previously treated with at least two approved TKIs; Part B: T315I mutation at screening and previously treated with at least one approved TKI, with no other effective and/or tolerable therapies available 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 5. Patient has adequate organ function
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria: 1. For Part A only: T315I or V299L mutation at any time prior to starting study treatment 2. Active infection that requires systemic drug therapy 3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of study drugs 4. Previous treatment with or known / suspected hypersensitivity to olverembatinib or any of its excipients 5. Previous treatment with or known / suspected hypersensitivity to bosutinib or any of its excipients 6. Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-Week MMR Rate (Part A) | 24 weeks | To compare the major molecular response (MMR) rate at 24 weeks for olverembatinib versus bosutinib |
| 24-Week MMR Rate (Part B) | 24 weeks | To evaluate the MMR rate by 24 weeks for olverembatinib in CML-CP patients with T315I mutation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 96-Week MMR Rate (Part A) | 96 weeks | To compare the major molecular response (MMR) rate at 96 weeks for olverembatinib versus bosutinib |
| 96-Week MMR Rate (Part B) | 96 weeks | To evaluate the major molecular response (MMR) rate by 96 weeks for olverembatinib in CML-CP patients with T315I mutation |
| Cytogenic Response Rate (Part A) | Through 96 weeks (i.e., at 24, 48, and 96 weeks) | To compare the complete cytogenic response rate at all scheduled data collection time points for olverembatinib vs. bosutinib. |
| Cytogenic Response Rate (Part B) | Through 96 weeks (i.e., at 24, 48, and 96 weeks) | To evaluate the complete cytogenic response rate at all scheduled data collection time points for olverembatinib in CML-CP patients with T315I mutation |
| Progression Free Survival (PFS) (Part A) | 5 years after the last patient received the first study dose | To compare duration of PFS (i.e., from the date of randomization to the earliest occurrence of documented disease progression to AP/BP or the date of death from any cause) for olverembatinib versus bosutinib |
| Progression Free Survival (PFS) (Part B) | 5 years after the last patient received the first study dose | To evaluate duration of PFS (i.e., from the date of enrollment to the earliest occurrence of documented disease progression to AP/BP or the date of death from any cause) for olverembatinib in CML-CP patients with T315I mutation |
| Overall Survival (OS) (Part A) | 5 years after the last patient received the first study dose | To compare OS (duration from date of randomization to date of death) for olverembatinib versus bosutinib |
| Overall Survival (OS) (Part B) | 5 years after the last patient received the first study dose | To evaluate OS (duration from date of randomization to date of death) for olverembatinib in CML-CP patients with T315I mutation |
| Number of participants with treatment-emergent and treatment-related adverse events as assessed by CTCAE v5.0 (Parts A and B) | 96 weeks after the last patient received the first study dose | According to CTCAE v5.0, the number and frequency of adverse events for test drug will be assessed. |
| Characterization of population pharmacokinetics of olverembatinib (Parts A and B) | At the end of Cycle 1 and Cycle 2 (each cycle is 28 days) | Blood samples will be collected to measure the plasma concentration of olverembatinib |
Countries
Australia, Belgium, Canada, France, Germany, India, Italy, Japan, Poland, Russia, Singapore, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAscentage Clinical Operations
PRINCIPAL_INVESTIGATORElias Jabbour, M.D.
M.D. Anderson Cancer Center
Outcome results
None listed