Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations

NCT07012447 | Recruiting Phase 2

• 1 other identifier: SZ-ETP01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of venetoclax combined with azacitidine in treating newly diagnosed early T-cell precursor (ETP)-like acute lymphoblastic leukemia (ALL), T-ALL with myeloid mutations, or T/myeloid mixed-phenotype acute leukemia (T/My-MPAL). Participant population: Patients aged ≥14 years diagnosed with ETP-like leukemia, T-ALL with myeloid mutations, or T/My-MPAL, regardless of sex/gender. The main question it aims to answer: Does venetoclax plus azacitidine achieve a significantly higher overall response rate (ORR: CR + CRi) compared to historical controls (54% vs. 90%) after two induction cycles? Comparison group: Researchers will compare ORR outcomes to historical data from conventional chemotherapy regimens to assess treatment superiority. Participants will:

• Receive two 28-day cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m²/day SC, D1-7).
• Undergo serial bone marrow biopsies, blood tests, and imaging (e.g., PET-CT) for response assessment.
• Follow dose adjustment protocols for toxicity management (e.g., neutropenia, thrombocytopenia).

Conditions

Early T Acute Lymphoblastic Leukemia; T-Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia, T/Myeloid, Nos

Keywords

Adverse risk; newly diagnosed; induction therapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) after two treatment cycles of induction therapy

  Rates of complete remission (CR), and complete remission with incomplete hematologic recovery (CRi)

  time from the date of enrollment to 2 cycles of induction before consolidation therapy（100 days）

Secondary Outcomes (5)

• OS: overall survival

  2 years

• LFS：leukemia-free survival

  2 years

• DOR: duration of remission

  2 years

• AE

  Within 60 days after treatment

• Volume of infused blood products

  Within 60 days

Study Arms (1)

Investigational ( venetoclax, azacytidine)

EXPERIMENTAL

Two cycles induction as venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7); Consolidation: For fit patients, if those with MRD (Minimal Residual Disease) are negative or refuse to undergo allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m² q12h, days 1-3) cytarabine-based therapy is administered for 3-4 cycles; if patients are MRD-positive, they undergo allo-HSCT. For unfit patients, each venetoclax combined with azacitidine treatment cycle is anticipated to be 28 days in length until progression of disease, although cycle delays may occur due to delayed blood count recovery.

Drug: Venetoclax; Drug: Azacitidine; Drug: Cytarabine

Interventions

Venetoclax DRUG

Orally by mouth

Also known as: Venclexta

Investigational ( venetoclax, azacytidine)

Azacitidine DRUG

Subcutaneous injection

Investigational ( venetoclax, azacytidine)

Cytarabine DRUG

Intravenous infusion

Also known as: Ara-C

Investigational ( venetoclax, azacytidine)

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• No gender restrictions
• Age ≥ 14 years
• Confirmed diagnosis of one of the following:
• ETP-like leukemia (CD7⁺, CD1a-, CD8-, with CD5 expression stratified as ETP-ALL ≤75% or Near-ETP-ALL \>75%) T-cell acute lymphoblastic leukemia (T-ALL) with myeloid mutations (including FLT3, DNMT3A, STAG2, IDH1/2, RUNX1, EZH2, WT1, ASXL1/2, SF3B1, TET2, BCOR, BCORL1, and MLL-PTD) T/myeloid mixed phenotype acute leukemia (T/My-MPAL) (with concurrent T-lineage and myeloid markers, e.g., cCD3⁺/mCD3⁺, CD7⁺, MPO⁺)
• Newly diagnosed patients without prior induction therapy Limited prior therapy allowed: hydroxyurea, dexamethasone, or low-dose cytarabine/venetoclax (cumulative dose \<0.5g), and leukocytapheresis
• Expected survival time ≥ 3 months
• Liver function: total bilirubin ≤ 2× ULN; ALT/AST ≤ 3× ULN (or ≤ 5× ULN if liver infiltration by leukemia is present) ; Renal function: endogenous creatinine clearance ≥ 30 ml/min; Cardiac function: left ventricular ejection fraction \> 45%
• Demonstrated capacity to understand the study and willingness to provide informed consent

You may not qualify if:

• Presence of recurrent genetic abnormalities such as t(8;21), t(15;17), inv(16)/t(16;16) leukemia
• Prior hypersensitivity to study drugs or compounds of similar chemical structure
• Active uncontrolled infections as determined by the investigator
• Active bleeding
• Recent history (within 1 year) of thrombosis, embolism, or cerebral hemorrhage
• Pregnancy, breastfeeding, or unwillingness to use contraception in women of childbearing potential
• Drug addiction or chronic alcoholism that could interfere with trial evaluation
• Psychiatric disorders or other conditions that would prevent obtaining informed consent or compliance with trial requirements
• Any condition deemed unsuitable for trial participation by the investigator

Sponsors & Collaborators

• yuejun Liu: lead

Study Sites (1)

Ethical Committee of the First Affliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Pyloric Stenosis, Hypertrophic

Interventions

venetoclax; Azacitidine; Cytarabine

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yue-jun Liu

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yue-jun Liu

CONTACT

008613915535177; liuyuejun@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: June 10, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)