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

Phase 2Not Yet RecruitingNCT07573670

The First Affiliated Hospital of Soochow University52 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Newly Diagnosed Mixed Phenotype Acute Leukemia

Eligibility

Sex: ALLMin age: 16 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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)

Time frame: From randomization to 2 cycles of induction before consolidation therapy（100 days）

Secondary Outcomes

MRD negativity rate

Bone marrow MRD \<0.01% detected by MFC

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From treatment initiation to the end of Induction

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts