Venetoclax-containing Therapy Combined With Microtransplant for Intermediate-risk and Higher MDS

NCT07238686 | Recruiting Phase 2

• 1 other identifier: VEN-MST for MDS
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety and efficacy of a Venetoclax and hypomethylating agent-based regimen combined with infusion of HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cells (GPBMC) in patients with intermediate-risk and higher myelodysplastic syndromes who are ineligible for allogeneic hematopoietic stem cell transplantation.

Conditions

Myelodysplastic Syndromes

Keywords

venetoclax; hypomethylating agent; GPBMC infusion; microtransplant; microtransplantation

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  OS is defined as the number of days from the date of study entry to the date of death.

  Measured up to 4 years after the last participant is enrolled

• Overall response rate (ORR)

  ORR is defined as complete remission (CR) (or CR equivalent) + partial remission (PR) + CR with limited count recovery (CRL) + CR with partial hematologic recovery (CRh) + hematologic improvement (HI) according to IWG 2023 criteria.

  Measured up to 2 years after the last participant is enrolled

Secondary Outcomes (7)

• Modified overall response (mOR)

  Measured up to 2 years after the last participant is enrolled

• Complete remission (CR)

  Measured up to 2 years after the last participant is enrolled

• Partial remission (PR)

  Measured up to 2 years after the last participant is enrolled

• CR with limited count recovery (CRL)

  Measured up to 2 years after the last participant is enrolled

• CR with partial hematologic recovery (CRh)

  Measured up to 2 years after the last participant is enrolled

Study Arms (1)

Cohort 1

EXPERIMENTAL

This cohort includes patients with intermediate-risk and higher MDS who are ineligible for or refuse allogeneic HSCT. Patients receive Venetoclax in combination with hypomethylating agent and HLA-mismatched donor GPBMC infusion. Treatment cycles are 28 days, repeated until disease progression or unacceptable toxicity.

Drug: Venetoclax; Drug: Azacitidine (AZA) or Decitabine (DAC); Biological: GPBMC infusion

Interventions

Venetoclax DRUG

Given PO. For the first cycle, dose of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3-14. For other cycles, dose of 400 mg on Days 1-14. Note: The dose should be reduced to 100-200 mg daily if concomitant azole antifungals are required.

Cohort 1

Azacitidine (AZA) or Decitabine (DAC) DRUG

AZA: Given SC. Dose of 75 mg/m² on Days 1-7 of each cycle. DAC: Given IV. Dose of 20 mg/m² on Days 1-5 of each cycle.

Cohort 1

GPBMC infusion BIOLOGICAL

HLA-mismatched donor GPBMCs are infused on Day 15.

Cohort 1

Eligibility Criteria

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

You may qualify if:

• Age \>=18 years, male or female, non-limited by race or ethnicity.
• Confirmed diagnosis of MDS according to the World Health Organization (WHO) 5th edition classification, based on histopathology and cytogenetics.
• Risk stratification according to the Revised International Prognostic Scoring System (IPSS-R) must place the patient in the intermediate-, high-, or very high-risk category.
• Not candidates for or refuse allogeneic hematopoietic stem cell transplantation.
• Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )\<= 3 × upper limit of normal(ULN), and total bilirubin \<= 1.5 × ULN.
• Adequate renal function including serum creatinine \<= 2 × ULN or CrCl\>= 40mL/min.
• LVEF measured by echocardiogram is within the normal range (LVEF \> 50%).
• The subject must have one donor who is \>= 18 years old and HLA matched at 0-7/10 loci (i.e., at least 3 HLA loci must be mismatched). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form.
• Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research.

You may not qualify if:

• Uncontrolled infection or hemorrhage.
• Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
• Uncontrolled autoimmune disease or requiring immunosuppression treatment.
• History of severe blood infusion reaction.
• Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
• Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements.
• Major surgery within 4 weeks prior to enrollment.
• Life-threatening illness other than MDS or uncontrolled intercurrent illness.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

Beijing, 100071, China

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

venetoclax; Azacitidine; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic 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

Study Officials

• Bo Cai, MD

  Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Cai, MD

CONTACT

+861066947168; caibo2008@163.com

Fei Peng, MD

CONTACT

+861066947180; pengfei0118@foxmail.com

Study Design

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

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 20, 2025
• Study Start: June 20, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: November 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)