Myelodysplastic Syndromes
Conditions
Keywords
venetoclax, hypomethylating agent, GPBMC infusion, microtransplant, microtransplantation
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.
Interventions
DRUGVenetoclax
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.
DRUGAzacitidine (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.
BIOLOGICALGPBMC infusion
HLA-mismatched donor GPBMCs are infused on Day 15.
Sponsors
Beijing 302 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Partial remission (PR) | Measured up to 2 years after the last participant is enrolled | 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. |
| CR with limited count recovery (CRL) | Measured up to 2 years after the last participant is enrolled | 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. |
| Modified overall response (mOR) | Measured up to 2 years after the last participant is enrolled | Modified OR is defined as CR+PR+CRL+CRh. |
| Progression-free survival (PFS) | Measured up to 4 years after the last participant is enrolled | 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. |
| Treatment-related mortality (TRM) | Measured up to 2 years after the last participant is enrolled | TRM is defined as the death related to treatment instead of disease progression. |
| CR with partial hematologic recovery (CRh) | Measured up to 2 years after the last participant is enrolled | 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%. |
| Complete remission (CR) | Measured up to 2 years after the last participant is enrolled | 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%. |
Countries
China
Contacts
Primary ContactBo Cai, MD
Backup ContactFei Peng, MD
Outcome results
None listed