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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: T/Myeloid MPAL | Experimental | Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
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| Cohort B: B/Myeloid MPAL | Experimental | Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; Blinatumomab: 9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCL-2 indibitor | Drug | Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral;
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| Measure | Description | Time Frame |
|---|---|---|
| Composite Complete Response (CRc) rate after 2 cycles of induction therapy | CRc = CR + CRi; CR: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, ANC ≥1.0×10⁹/L, PLT ≥100×10⁹/L; CRi: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, incomplete hematologic recovery (ANC <1.0×10⁹/L or PLT <100×10⁹/L) | From randomization to 2 cycles of induction before consolidation therapy（100 days） |
| Measure | Description | Time Frame |
|---|---|---|
| MRD negativity rate | Bone marrow MRD <0.01% detected by MFC | From randomization to 2 cycles of induction before consolidation therapy（100 days） |
| NGS-MRD negativity rate | NGS-MRD can not detected by IgH/TCR NGS (NGS-based MRD will be incorporated as an exploratory complementary assay in patients with trackable clonotypic rearrangements at diagnosis) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jing Lu Doctor | Contact | 86+0512-67781137 | gloriajlu@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Suning Chen | The First Affiliated Hospital of Soochow University Principal Investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | 215000 | China |
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Two independent cohorts based on immunophenotype： Cohort A (T/Myeloid MPAL) Cohort B (B/Myeloid MPAL)
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| Azacitidine (AZA) | Drug | 75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles |
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| Blinatumomab | Drug | 9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion |
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| From randomization to 2 cycles of induction before consolidation therapy（100 days）, and test Every 3 months during follow-up |
| CR1 bridge-to-allo-HSCT rate | Proportion of subjects who achieve CR/CRi and successfully receive allo-HSCT within 2-3 cycles | Up to 6 months after enrollment |
| Overall Survival (OS) | Time from C1D1 to death from any cause; data censored at last follow-up for surviving subjects | From the time from randomization to time for up to 2 years |
| Event-Free Survival (EFS) | Time from C1D1 to first event (no CRc after 2 cycles, morphological/extramedullary relapse, disease progression, off-protocol anti-leukemia therapy, death from any cause); data censored at last follow-up for event-free subjects | From the time from randomization to time for up to 2 years |
| Relapse-Free Survival (RFS) | Time from first CR/CRi to relapse or death from any cause; relapse defined as bone marrow blasts ≥5%, extramedullary disease, peripheral blasts, or molecular MRD ≥10-⁴ in previously MRD-negative patients;data censored at last follow-up for relapse-free subjects | From the time from randomization to time for up to 2 years |
| 100-day Non-Relapse Mortality (100-day NRM) | Proportion of deaths from non-relapse causes within 100 days of diagnosis | Up to 100 days after initial MPAL diagnosis |
| Incidence of grade ≥3 adverse events (AEs) | Type, frequency and severity of grade ≥3 AEs graded by CTCAE v5.0 | From treatment initiation to the end of Induction |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C510808 | blinatumomab |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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