Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, Ph+ ALL
Conditions
Keywords
Ph+ ALL, Olverembatinib, Acute lymphoblastic leukemia, Bcr-Abl Tyrosine Kinase
Brief summary
A global multicenter, open-label, randomized and registrational Phase 3 study to evaluate efficacy and safety of olverembatinib combined with chemotherapy versus investigator's choice of tyrosine kinase inhibitor (TKI) combined with chemotherapy in subjects with newly-diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL).
Detailed description
Comparing efficacy and safety of olverembatinib in combination with chemotherapy (investigational arm) vs. investigator's choice of TKI in combination with chemotherapy (control arm).
Interventions
DRUGOlverembatinib
Oral (PO) once every other day (QOD).
DRUGInvestigator's choice of TKI
Oral (PO) once daily (QD).
Sponsors
Ascentage Pharma Group Inc.
Guangzhou Healthquest Pharma Co., Ltd
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
1. Newly diagnosed Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) 2. Expected survival of at least 3 months 3. ECOG ≤ 2 4. Adequate organ function
Exclusion criteria
1. A history of chronic myeloid leukemia (CML) 2. Clinical manifestations of central nervous system (CNS) leukemia or ALL extramedullary infiltration, except lymphadenopathy or hepatosplenomegaly 3. Previous or current clinical CNS diseases 4. Autoimmune diseases that may involve the CNS 5. Use of therapeutic doses of anticoagulants and/or antiplatelet agents; low doses of anticoagulants or antiplatelet agents are allowed 6. Use a therapeutic drug that has drug interaction with the investigational drug due to other diseases within 7 days or within 5 half-lives (whichever is shorter) prior to the first receipt of the investigational drug 7. Uncontrolled heart diseases 8. Any venous thromboembolism in the 6 months prior to randomization, including but not limited to deep vein thrombosis (DVT) or pulmonary embolism 9. Use of prohibited drugs 10. Disease or medical condition that is unstable or may affect its safety or compliance with the study 11. Use of medications known to cause prolonged QT interval 12. Active infections requiring systemic treatment 13. Disease that severely affects the oral administration and absorption of drugs, or an active gastrointestinal ulcer 14. Contraindications to the use of glucocorticoids 15. Bleeding disorders unrelated to ALL 16. Plan to undergo major surgery 17. Allergy to drug ingredients, excipients, or their analogues in the study 18. Female subjects who are pregnant or breastfeeding or expect to become pregnant during the study period 19. Other malignant tumors within 2 years 20. Any symptom or illness that may interfere with the evaluation of the efficacy and safety of the investigational drug, or any other condition or condition that is not appropriate for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease Negative CR Rate | Cycle 1 to Cycle 3 (each cycle is 28 days) | The minimal residual disease negative CR rate of olverembatinib combined with chemotherapy versus investigator's choice of TKI combined with chemotherapy in subjects with newly diagnosed Ph+ALL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | Baseline up to 3 to 6 years | EFS is defined as the time from study randomization to the date of treatment failure (ITF), relapse from CR, or death from any cause, whichever comes first. |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. | Through study completion (approximately 2 years) | According to CTCAE v5.0, the number and frequency of adverse events of test drug will be assessed. |
| Plasma concentrations of olverembatinib | Cycle 1 to Cycle 3 (each cycle is 28 days) | Blood samples will be collected to measure the plasma concentration of olverembatinib. |
| FACT-Leu (Functional Assessment of Cancer Therapy - Leukemia) Score | Through study completion (approximately 2 years) | To evaluate health-related Quality of Life (HR-QoL) in patients treated with olverembatinib plus chemotherapy. |
Countries
Australia, China, Czechia, France, Italy, Romania, Singapore, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAscentage Clinical Operations
PRINCIPAL_INVESTIGATORElias Jabbour, M.D.
M.D. Anderson Cancer Center
PRINCIPAL_INVESTIGATORWeili Zhao, M.D., Ph.D.
Shanghai Jiaotong University School of Medicine Ruijin Hospital
PRINCIPAL_INVESTIGATORSuning Chen, M.D., Ph.D.
First Affiliated Hospital of Suzhou Medical College
Outcome results
None listed