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

NCT07573670 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: MPAL-1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Newly Diagnosed Mixed Phenotype Acute Leukemia

Keywords

Newly diagnosed Mixed Phenotype Acute Leukemia; Bcl-2 inhibitor (Sonrotoclax)

Outcome Measures

Primary Outcomes (1)

• 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）

Secondary Outcomes (8)

• MRD negativity rate

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

• NGS-MRD negativity rate

  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

  Up to 6 months after enrollment

• Overall Survival (OS)

  From the time from randomization to time for up to 2 years

• Event-Free Survival (EFS)

  From the time from randomization to time for up to 2 years

Study Arms (2)

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.

Drug: BCL-2 indibitor; Drug: Azacitidine (AZA)

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.

Drug: BCL-2 indibitor; Drug: Azacitidine (AZA); Drug: Blinatumomab

Interventions

BCL-2 indibitor DRUG

Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; * 2 cycles.

Also known as: Sonrotoclax

Cohort A: T/Myeloid MPAL; Cohort B: B/Myeloid MPAL

Azacitidine (AZA) DRUG

75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles

Also known as: Azacitidine

Cohort A: T/Myeloid MPAL; Cohort B: B/Myeloid MPAL

Blinatumomab DRUG

9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion

Cohort B: B/Myeloid MPAL

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

MeSH Terms

Interventions

Azacitidine; blinatumomab

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Suning Chen

  The First Affiliated Hospital of Soochow University Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Lu Doctor

CONTACT

86+0512-67781137; gloriajlu@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: Two independent cohorts based on immunophenotype： Cohort A (T/Myeloid MPAL) Cohort B (B/Myeloid MPAL)

Study Record Dates

• First Submitted: April 26, 2026
• First Posted: May 7, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 7, 2026

Record last verified: 2026-05

Locations

CN (1)