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
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Overall survival (OS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Azacitidine (AZA) or Decitabine (DAC) (Drug)
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.
Intervention: GPBMC infusion (Biological)
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.
Intervention: Venetoclax (Drug)
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: Measured up to 4 years after the last participant is enrolled
OS is defined as the number of days from the date of study entry to the date of death.
Overall response rate (ORR)
Time Frame: Measured up to 2 years after the last participant is enrolled
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.
Secondary Outcomes
- Treatment-related mortality (TRM)(Measured up to 2 years after the last participant is enrolled)
- 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)
- Progression-free survival (PFS)(Measured up to 4 years after the last participant is enrolled)