VA Induction and Bridging Transplantation for Hypoplastic/Secondary AML

A Multicenter, Single-arm Clinical Study of Venetoclax Combined With Azacitidine Induction and Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Hypoplastic or Secondary Acute Myeloid Leukemia

The purpose of this study is to explore the efficacy and safety of venetoclax combined with azacitidine（VA) induction followed by bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hypoplastic and secondary acute myeloid leukemia (AML).

Study Overview

• Status: Not yet recruiting
• Conditions: Secondary AML (Adult); Hypoplastic Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax (VEN); Drug: Azacitidine (AZA); Procedure: Allo-HSCT

Detailed Description

Under the traditional intensive chemotherapy model, patients with hypoplastic or secondary acute myeloid leukemia (AML) often have poor bone marrow reserve and prolonged post-chemotherapy cytopenia, leading to high early mortality, low remission rates, and short median survival. To address this, the use of venetoclax combined with a hypomethylating agent (the VA regimen) as induction therapy significantly improves complete remission (CR) and overall survival (OS). Subsequent bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation further enhances OS and relapse-free survival (RFS). This combined strategy demonstrates a clear synergistic effect: the VA regimen effectively increases the transplantation rate, and for patients with relapsed/refractory (R/R) AML, a low-intensity regimen followed by bridging transplantation is non-inferior to traditional intensive chemotherapy, achieving a "1+1>2" therapeutic benefit. Therefore, the investigators conducted a prospective study to evaluate the efficacy and safety of VA regimen induction followed by allo-HSCT in patients with hypoplastic and secondary AML.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhen Shen, Doctor; Phone Number: 0512-67976802; Email: zhenshen96@sina.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Previously untreated acute myeloid leukemia (AML) diagnosed according to the 2022 ELN guidelines. Patients with isolated extramedullary disease (i.e., no evidence of AML in bone marrow or peripheral blood) are not eligible.
3. Bone marrow biopsy demonstrating cellularity <20% or concurrent myelofibrosis; Or a prior history of an antecedent hematologic disorder, radiotherapy/chemotherapy-related history, or presence of myelodysplasia-related changes (AML-MRC according to WHO-HEAM5).
4. The patient is deemed suitable for allogeneic hematopoietic stem cell transplantation as assessed by the treating physician.
5. Adequate organ function, defined as follows: a. Good liver function: serum total bilirubin ≤2.0 × upper limit of normal (ULN); if considered due to Gilbert's disease or leukemia, serum total bilirubin <3.0 × ULN. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemia. b. Good renal function: serum creatinine ≤2.0 × ULN or creatinine clearance >30 mL/min calculated using the Cockcroft-Gault formula. c. No history of chronic lung disease and no dyspnea. Otherwise, documented diffusing capacity of the lung for carbon monoxide ≤40% (adjusted for hemoglobin if available) and forced expiratory volume in 1 second/forced vital capacity ≥50%.
6. ECOG performance status score 0-2.
7. Ability to understand and voluntarily sign informed consent.
8. Women of childbearing potential must have a negative serum pregnancy test before initiation of study treatment.

Exclusion Criteria:

1. Prior treatment for AML, except non-cytotoxic therapy given to stabilize disease.
2. White blood cell count ≥10×10⁹/L, or presence of proliferation-associated gene mutations such as FLT3.
3. Favorable risk group according to the 2022 ELN prognostic stratification, e.g., t(8;21), inv(16)/t(16;16), NPM1 mutation, or CEBPA bZIP in-frame mutation.
4. No suitable stem cell donor available.
5. Acute promyelocytic leukemia (APL).
6. Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
7. Life-threatening immediate complications of leukemia, such as uncontrolled bleeding, hypoxic pneumonia, sepsis, and/or disseminated intravascular coagulation (DIC). Expected survival <12 weeks.
8. Prior allogeneic hematopoietic stem cell transplantation for a hematologic disorder.
9. Current use of strong CYP3A4 inducers or narrow-therapeutic-window CYP3A4 substrates; enrollment is allowed only if these drugs can be switched to alternatives ≥5 half-lives before the first dose of study treatment.
10. Active, uncontrolled systemic fungal, bacterial, or viral infection despite appropriate antibiotic, antiviral, or other therapy.
11. Known infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) that cannot be controlled by therapy.
12. Another active malignancy, unless the patient has been disease-free for ≥5 years before initiation of study treatment. However, patients with the following history/concurrent conditions or similar indolent cancers are eligible: Basal cell or squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Prostate cancer found incidentally on histology.
13. Significant active cardiac disease within 6 months before initiation of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
14. Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg).
15. Dysphagia, short-bowel syndrome, gastroparesis, or other conditions that limit oral intake or gastrointestinal absorption.
16. Known history of progressive multifocal leukoencephalopathy (PML).
17. Known hypersensitivity to any component of venetoclax or azacitidine.
18. Female patient who is pregnant or breastfeeding.
19. Any other medical or psychological condition that, in the investigator's opinion, could interfere with the patient's ability to sign informed consent or participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: A; VA induction+Allo-HSCT consolidation

Drug: Venetoclax (VEN); Venetoclax was administered at 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-28 of cycle 1.; Drug: Azacitidine (AZA); Azacitidine was administered at 75 mg/m² on days 1-7 of cycle 1.; Procedure: Allo-HSCT; All patients proceeded directly to allogeneic HSCT after cycle 1, regardless of remission. Myeloablative or intensified conditioning was preferred; reduced-intensity conditioning was allowed for intolerant patients. Donor source and transplant type were not restricted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the date of diagnosis to death due to any cause.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate（CRR）	Bone marrow blasts <5%, absence of extramedullary disease, no circulating blasts, peripheral blood neutrophil count ≥1.0×10⁹/L, platelet count ≥100×10⁹/L, independent of transfusion or growth factor support.	Day 28 of induction therapy and 56 days post-transplantation
Composite Complete Remission Rate (CCRR)	The proportion of patients achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh).	Day 28 of induction therapy and 56 days post-transplantation
Disease-free Survival (DFS)	Time from achieving disease remission to disease relapse or death from any cause.	2 year
GVHD-free and Relapse-free Survival (GRFS)	Time from transplant date to the first occurrence of grade III-IV acute GVHD, chronic GVHD requiring systemic treatment, disease relapse, or death from any cause.	2 year
Cumulative Incidence of Relapse (CIR)	Time from transplant date to disease relapse.	2 year
Non-relapse Mortality (NRM)	Time from transplant date to death due to non-relapse/progression causes.	2 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Ruijin Hospital North Shanghai Jiao Tong University School of Medicine; Nanfang Hospital, Southern Medical University
• Investigators: Principal Investigator: Suning Chen, Doctor, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 7, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Venetoclax; Azacitidine; Allo-HSCT
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: 2026531; 09021420250003 (Other Grant/Funding Number: Suzhou University Affiliated First Hospital 'Yanzhen Lingfei' Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No