Acute Myeloid Leukemia, Lisaftoclax
Conditions
Keywords
Acute myeloid leukemia; Lisaftoclax
Brief summary
This is a phase II/III, multicenter, randomized, three-arm, open-label, parallel controlled trial. The primary objective of this study is to compare the 2-years EFS rate of the LDA, LHAA, and DA regimens in newly diagnosed patients with low-risk acute myeloid leukemia who are eligible for intensive chemotherapy.
Interventions
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + homoharringtonine (2 mg/m², qd, intramuscular injection or iv infusion, D1-5) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-5) + aclarubicin (12 mg/m², maximum 20 mg, iv, D1-5).
Daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
DRUGLisaftoclax+cytarabine
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
Lisaftoclax (400 mg, orally, D1-7) + azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Sponsors
First Affiliated Hospital of Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification; 2. Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification; 3. Age 18-65 years; 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; 5. Adequate hepatic and renal function: total bilirubin ≤2 mg/dL (35 μmol/L); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2× the upper limit of normal; serum creatinine ≤177 μmol/L; 6. Normal cardiac function, defined as left ventricular ejection fraction (LVEF) \>50%; 7. Life expectancy ≥3 months; 8. Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.
Exclusion criteria
1. Acute promyelocytic leukemia; 2. Central nervous system involvement by leukemia; 3. History of other malignancies within the past 5 years; 4. Positive for human immunodeficiency virus (HIV); 5. Presence of any other serious medical condition that may limit study participation, including advanced infections, uncontrolled diabetes mellitus, severe cardiac insufficiency, or angina; 6. Ineligible for intensive chemotherapy due to poor general condition; 7. Pregnant or breastfeeding women; 8. Inability to understand or comply with the study protocol; 9. Inability to take oral medication or presence of malabsorption syndrome; 10. Prior treatment with B-cell lymphoma 2 (BCL-2) inhibitors or hypomethylating agents, or current participation in any other investigational drug study; 11. Inability or unwillingness to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year event-free survival (EFS) rate | from randomization up to 2 years after randomization | defined as the proportion of patients remaining free of treatment failure, hematologic relapse, MRD relapse, or death within 2 years after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) rate after 1/2 treatment cycles | At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days) | defined as the proportion of patients achieving complete response (CR) after the first or second cycle of induction chemotherapy. |
| Composite Complete Response (CRc) rate after 1/2 treatment cycles | At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days) | defined as the proportion of patients achieving CRc after the first or second cycle of induction chemotherapy. |
| Minimal residual disease (MRD) negativity rate after 1-2 cycles of induction chemotherapy | At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days) | defined as the the proportion of patients with negative minimal residual disease (MRD) among patients who achieve complete remission after 1-2 cycles of induction chemotherapy |
| 2-year overall survival rate (OS) | from randomization up to 2 years | defined as the proportion of patients who were still alive from the time of randomization for the last patient until 24 months later |
| 2-year relapse-free survival (RFS) rate | from the date of complete remission (CR/CRi) up to 2 years after achieving response | defined as the proportion of patients who achieved complete response (CR) or complete remission with incomplete hematologic recovery (CRi) and remained alive without disease relapse within 2 years after achieving response. |
| Safety and Tolerability | up to 24 months | defined as the number of participants with adverse events and serious adverse events as assessed by NCI CTCAE v5.0 |
Countries
China
Outcome results
None listed