Clinical Study of Venetoclax Combined With Azacitidine as Bridging Therapy Prior to Hematopoietic Stem Cell Transplantation in Patients With Higher-Risk Myelodysplastic Syndromes

Official title

A Single-Arm, Prospective Clinical Study of Venetoclax Combined With Azacitidine Followed by Bridging Transplantation in Patients With High-Risk Myelodysplastic Neoplasms With Increased Blasts 2 (MDS-IB2)

Overview

A Single-Arm, Prospective Clinical Study of Venetoclax Combined with Azacitidine Followed by Bridging Transplantation in Patients with High-Risk Myelodysplastic Neoplasms with Increased Blasts 2 (MDS-IB2)

Detailed description

This is a single-center, single-arm, prospective study investigating pre-transplant bridging therapy in patients aged ≥18 years with higher-risk MDS-IB2. The study plans to enroll 46 eligible patients. Participants will receive Venetoclax combined with Azacitidine, administered in 28-day cycles for 1 to 2 cycles. Treatment response will be assessed according to the IWG 2023 HR-MDS response criteria.Patients achieving modified Composite Complete Remission (mCRc: CR or CR-equivalent + CRL + CRh) after Cycle 1 will proceed directly to transplantation. Patients not achieving mCRc will receive a second cycle of therapy. All patients will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months after completing Cycle 2, regardless of mCRc status. Patients unable to proceed to transplantation will receive standard institutional care and undergo follow-up.

Interventions

• Drug VEN (Venetoclax)
  Enrolled patients will receive: Venetoclax: 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3-14. Azacitidine: 75 mg/m² on Days 1-7. Cycle duration: 28 days Total cycles: 1 to 2 cycles

Primary outcome measures

• 2-Year Relapse-Free Survival(2-RFS) [Time frame: From date of index treatment to death, disease progression, or end of study, whichever came first, assessed up to 24 months.]

Secondary outcome measures (3)

• Overall Survival (OS) [Time frame: From date of index treatment to death, disease progression, or end of study, whichever came first, assessed up to 48 months.]
• Cumulative Relapse Rate (CIR) [Time frame: rom date of index treatment to death, disease progression, or end of study, whichever came first, assessed up to 24 months.]
• Composite Complete Response Rate（mCRc） [Time frame: Through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Newly diagnosed MDS confirmed by morphological and immunophenotypic analysis of bone marrow；
• Age ≥18 years, any gender；
• Bone marrow blasts ≥10%；
• IPSS-R score >4.5；
• ECOG performance status 0-2；
• Scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT)；
• Adequate major organ function：

• Cardiac: LVEF ≥50%
• Hepatic: Bilirubin ≤1.5×ULN
• AST/ALT ≤2.5×ULN
• Renal: Creatinine clearance ≥60 mL/min；
• Written informed consent provided by the patient or legally authorized representative.

Exclusion criteria

• Extramedullary disease involvement；
• Hypersensitivity to any study drugs；
• Clinically significant hepatic/renal dysfunction exceeding inclusion thresholds；
• Severe cardiac disease, including congestive heart failure, myocardial infarction, and cardiac insufficiency;
• Concurrent malignant tumors of other organs, which can be enrolled if previously cured;
• Active tuberculosis or HIV infection;
• Concomitant hematologic disorders;
• Pregnancy or lactation;
• Inability to comply with protocol requirements;
• Concurrently participating in other clinical studies.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07047183 · 2025-HS-061

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗