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

Phase 2 Study of Venetoclax-containing Therapy in Combination With HLA-mismatched Mobilized Peripheral Blood Mononuclear Cell Infusion for Intermediate-risk and Higher Myelodysplastic Syndromes

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine (AZA) or Decitabine (DAC); Biological: GPBMC infusion

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bo Cai, MD; Phone Number: +861066947168; Email: caibo2008@163.com
• Study Contact Backup: Name: Fei Peng, MD; Phone Number: +861066947180; Email: pengfei0118@foxmail.com

Study Locations

• China
  • Beijing, China, 100071
    • Recruiting
    • Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
    • Contact: Bo Cai, MD; Phone Number: +861066947168; Email: caibo2008@163.com
    • Principal Investigator: Bo Cai, MD
    • Contact: Fei Peng, MD; Phone Number: +861066947180; Email: pengfei0118@foxmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.
• Donor inclusion criteria: The donor meets the institution's criteria for related peripheral blood hematopoietic stem cell donors. The donor must be able to tolerate the cell separation and collection process, and sign the Informed Consent Form.

Exclusion Criteria:

• 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.

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: Cohort 1; 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; 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.; Drug: Azacitidine (AZA) or Decitabine (DAC); 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.; Biological: GPBMC infusion; HLA-mismatched donor GPBMCs are infused on Day 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial remission (PR)	PR is defined as decrease of at least 50% in the percentage of blasts still ≥5% in the bone marrow, peripheral blood neutrophil count > 1 × 109/L, platelet count > 100 × 109/L, Hb ≥10 g/dL.	Measured up to 2 years after the last participant is enrolled
Modified overall response (mOR)	Modified OR is defined as CR+PR+CRL+CRh.	Measured up to 2 years after the last participant is enrolled
Treatment-related mortality (TRM)	TRM is defined as the death related to treatment instead of disease progression.	Measured up to 2 years after the last participant is enrolled
Complete remission (CR)	CR is defined as absolute neutrophil count > 1 × 109/L, platelet count > 100 × 109/L, Hb ≥10 g/dL, bone marrow with < 5% blasts, and PB blasts 0%.	Measured up to 2 years after the last participant is enrolled
CR with limited count recovery (CRL)	CRL is defined as bone marrow with less than 5% blasts, PB blasts 0%, and PB only meeting 1 or 2 of the following: absolute neutrophil count > 1 × 109/L, platelet count > 100 × 109/L, Hb ≥10 g/dL.	Measured up to 2 years after the last participant is enrolled
CR with partial hematologic recovery (CRh)	CRh is defined as bone marrow with less than 5% blasts, and PB not meeting criteria for CR or CRL, no Hb threshold required, platelets ≥50 × 109/L, neutrophils ≥0.5 × 109/L, blasts 0%.	Measured up to 2 years after the last participant is enrolled
Progression-free survival (PFS)	PFS is defined as the number of days from the date of study entry to the date of the first of the following events: progressed disease; relapse from CR (or CR equivalent), PR, CRL, CRh, or HI; death from any cause.	Measured up to 4 years after the last participant is enrolled

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Investigators: Principal Investigator: Bo Cai, MD, Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Estimated): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: venetoclax; microtransplantation; microtransplant; hypomethylating agent; GPBMC infusion
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Decitabine; Azacitidine; venetoclax
• Other Study ID Numbers: VEN-MST for MDS

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