Venetoclax-based therapy plus microtransplant for intermediate- or higher-risk 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 trial tests whether adding HLA-mismatched donor G-CSF–mobilized blood-cell infusions to venetoclax combined with a hypomethylating agent can help adults with intermediate- or higher-risk myelodysplastic syndromes who are not candidates for stem-cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing 302 Hospital (Academic / other)
• Locations: 1 site (Beijing)
• Trial ID: NCT07238686 on ClinicalTrials.gov

What this trial studies

This Phase II interventional protocol gives adults with IPSS-R intermediate-, high-, or very-high–risk MDS a regimen of venetoclax together with either azacitidine or decitabine, plus infusions of HLA‑mismatched G-CSF–mobilized peripheral blood mononuclear cells (GPBMC) from an identified donor. Treatment cycles, clinical and laboratory safety monitoring, and disease-response assessments are performed while patients are followed for efficacy and adverse events. The study targets patients who are ineligible for allogeneic hematopoietic stem-cell transplantation and requires an available donor with specified HLA mismatch criteria. Outcomes include safety, hematologic responses, and measures of disease control over the follow-up period.

Who should consider this trial

Good fit: Adults (≥18) with WHO-classified MDS at IPSS‑R intermediate, high, or very high risk who are not candidates for or refuse allo‑HCT, meet the study's liver, kidney, and cardiac-function criteria, and have an available donor (≥18 years) with at least three HLA loci mismatched are ideal candidates.

Not a fit: Patients with lower-risk MDS, those who are eligible for standard allogeneic transplant, individuals with significant hepatic, renal, or cardiac dysfunction, or those lacking an appropriate donor are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combination could improve response rates, blood counts, and delay progression for patients with higher-risk MDS who cannot undergo allogeneic transplant.

How similar studies have performed: Venetoclax plus hypomethylating agents has shown activity in related myeloid malignancies and microtransplantation has been reported in prior series, but combining venetoclax + HMA with GPBMC microtransplant is a novel approach with limited published data.

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.
* 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.

Where this trial is running

Beijing

• Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Bo Cai, MD — Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
• Study coordinator: Bo Cai, MD

Conditions Myelodysplastic Syndromes; venetoclax; hypomethylating agent; GPBMC infusion; microtransplant; microtransplantation