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

NCT ID: NCT07238686

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-20
• Study Completion Date: 2031-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: 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.

Azacitidine (AZA) or Decitabine (DAC)

Intervention Type: 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.

GPBMC infusion

Intervention Type: BIOLOGICAL

HLA-mismatched donor GPBMCs are infused on Day 15.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

GPBMC infusion

HLA-mismatched donor GPBMCs are infused on Day 15.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bo Cai, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Bo Cai, MD

Role: CONTACT

caibo2008@163.com

+861066947168

Fei Peng, MD

Role: CONTACT

pengfei0118@foxmail.com

+861066947180

Facility Contacts

Bo Cai, MD

Role: primary

caibo2008@163.com

+861066947168

Fei Peng, MD

Role: backup

pengfei0118@foxmail.com

+861066947180

Other Identifiers

VEN-MST for MDS

Identifier Type: -

Identifier Source: org_study_id