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

Yehui Tan

Status and phase: Enrolling; Phase 2

Conditions: Transplantation; Myelodysplastic Neoplasms

Treatments: Drug: VEN (Venetoclax)

Study type: Interventional

Funder types: Other

Identifiers

NCT07047183

2025-HS-061

Details and patient eligibility

About

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)

Full 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.

Enrollment: 46 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Newly diagnosed MDS confirmed by morphological and immunophenotypic analysis of bone marrow；

2. Age ≥18 years, any gender；

3. Bone marrow blasts ≥10%；

4. IPSS-R score >4.5；

5. ECOG performance status 0-2；

6. Scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT)；

7. Adequate major organ function：

   • Cardiac: LVEF ≥50%
   • Hepatic: Bilirubin ≤1.5×ULN
   • AST/ALT ≤2.5×ULN
   • Renal: Creatinine clearance ≥60 mL/min；

8. Written informed consent provided by the patient or legally authorized representative.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

46 participants in 1 patient group

venetoclax + Azacitidine

Experimental group

Treatment:

Drug: VEN (Venetoclax)