A Phase 2 Study of Bcl-2 Inhibitor Combined With Azacitidine for Newly Diagnosed Mixed Phenotype Acute Leukemia

A Prospective, Open-Label, Single-Arm, Two-Cohort Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Bcl-2 Inhibitor Combined With Azacitidine in the Treatment of Newly Diagnosed Mixed Phenotype Acute Leukemia

This is a prospective, open-label, single-arm, two-cohort Phase 2 clinical study designed to evaluate the efficacy and safety of Bcl-2 Inhibitor combined with azacitidine (with blinatumomab added in B/myeloid subtype) in patients with newly diagnosed mixed phenotype acute leukemia (MPAL). Eligible subjects are divided into two cohorts based on immunophenotype: Cohort A (T/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine, and Cohort B (B/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine + blinatumomab. The treatment cycle is 28 days, with the primary efficacy endpoint assessed after 2 cycles of induction therapy. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy.The total enrollment period is 24 months, and all subjects will be followed up for at least 24 months from the first day of the first cycle (C1D1).

The primary objective is to evaluate the composite complete response (CRc) rate after 2 cycles of induction therapy , and the secondary objectives include evaluating measurable residual disease (MRD) negativity rate, bridge-to-allogeneic hematopoietic stem cell transplantation (allo-HSCT) rate in first complete response (CR1), overall survival(OS),Event-Free Survival(EFS),Relapse-Free Survival(RFS) and Safety.

Inclusion Criteria:

1. Aged 16 to 70 years old
2. Newly diagnosed MPAL confirmed by the 2022 WHO/ICC classification criteria for hematopoietic and lymphoid neoplasms
3. Previously untreated; use of glucocorticoids or hydroxyurea for ≤7 days to control tumor burden before enrollment is allowed, no other systemic anti-leukemia therapy
4. ECOG performance status score 0-3
5. No severe combined heart, brain, lung, liver or kidney disease, judged by the investigator to tolerate the study regimen
6. Able to understand and voluntarily sign a written informed consent form

Exclusion Criteria:

1. BCR::ABL-positive MPAL patients
2. Presence of active, uncontrolled infection
3. Known uncontrolled active central nervous system leukemia (CNSL)
4. Life-threatening extramedullary disease requiring urgent radiotherapy or surgical debulking
5. Severe cardiac insufficiency with left ventricular ejection fraction (LVEF) <40%
6. Previous receipt of systemic anti-leukemia therapy
7. Pregnant or lactating female subjects
8. Judged by the investigator to be ineligible for the study for other reasons