Allogeneic Hematopoietic Stem Cell Transplantation, TP53-mutated MDS and AML
Conditions
Keywords
TP53 mutant myeloid tumors, allogeneic hematopoietic cell transplantation.
Brief summary
This study aims to explore the safety and efficacy of selinexor combined with azacitidine for maintenance therapy in TP53 mutant AML/MDS patients following transplantation.
Detailed description
This research targets high-risk recurrence patients with TP53 mutations in AML/MDS, administering low-dose azacitidine combined with selinexor for maintenance treatment post-allo-HCT (Allogeneic Hematopoietic Cell Transplantation). The goal is to observe the safety and tolerability of this drug combination as maintenance therapy post-transplant. The primary outcome measure will be post-transplant recurrence rate and non-relapse survival rate, while secondary outcomes include overall survival and non-relapse mortality. Previous studies have indicated that azacitidine and selinexor are safe and effective in maintenance therapy for AML/MDS. This study aims to reduce the risk of recurrence and prolong disease-free survival.
Interventions
DRUGMaintenance Therapy with Selinexor and Azacitidine
1. Selinexor: Oral administration in 4 cycles: \- Dose Escalation Phase: Cohort 1: Selinexor, 20 mg, twice a week for 2 weeks Cohort 2: Selinexor, 40 mg, twice a week for 2 weeks Cohort 3: Selinexor, 60 mg, twice a week for 2 weeks \- Dose Expansion: MTD/RP2D will be determined based on safety. 2. Azacitidine: 35 mg/m² for 5 days.
Sponsors
Daihong Liu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* (1) Voluntary participation in the clinical study: Participant or legal guardian understands and signs the Informed Consent Form (ICF) and is willing to comply with all trial procedures. (2) Age below 75 years at screening; gender not restricted. (3) Diagnosed with AML or MDS with TP53 mutation (VAF ≥ 2%) and post-allo-HCT. (4) No severe allergic constitution. (5) Liver function: ALT and AST ≤ 2.5 times the upper limit of normal, bilirubin ≤ 2 times the upper limit of normal. (6) Renal function: creatinine ≤ upper limit of normal. (7) No uncontrolled infections or severe psychiatric disorders. (8) ECOG performance score of 0-3; life expectancy of 4 months or more. (9) Peripheral blood counts for granulocytes and platelets.
Exclusion criteria
* (1) Patients with known allergies or contraindications to the study drugs. (2) Pregnant or breastfeeding women. (3) Patients with uncontrolled active infections or active GVHD. (4) Patients with a long history of smoking or alcohol abuse affecting trial outcome evaluation. (5) Patients with psychiatric disorders or conditions preventing informed consent, unable to comply with treatment and assessment requirements. (6) Patients who underwent major surgery on important organs less than 6 weeks prior. (7) Abnormal liver function: ALT or AST \> 2.5 times the upper limit of normal; bilirubin \> 2 times the upper limit of normal; renal function: creatinine \> upper limit of normal. (8) Patients deemed unsuitable for this clinical trial by the investigator (e.g., poor compliance, substance abuse).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease relapse | 1 year after transplantation | The definition of disease relapse: After remission, patients present with one of the following three conditions: (1) ≥5% of primary lymphocytes and immature lymphocytes in the bone marrow; (2) Extramedullary leukemia occurs; (3) Leukemia cells were found in peripheral blood smears. The definition of MRD recurrence: Leukemia cells are detected by flow cytometry or molecular biology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-relapse mortality (NRM) | 1 year after transplantation | From the first day after stem cell infusion to the last follow-up time, the number of NRM patients/the total number of cases ×100%. Death not caused by recurrence in the CR state. |
| Overall survival (OS) | 1 year after transplantation | The time from transplantation to death of any cause or the last follow-up day. |
| Progress-free survival (PFS) | 1 year after transplantation | The time from the date of transplantation to the recurrence of leukemia or death for any reason. |
| Drug-related adverse events | 1 month after the last maintenance treatment ends | All adverse events with a causal relationship to the study intervention (Selinexor + Azacitidine), assessed by investigators according to CTCAE v5.0 criteria. |
| Measurable Residual Disease (MRD) in bone marrow | 1 year after transplantation | Quantitative assessment of residual leukemic cells using: FCM-MRD and TP53 mutation NGS testing |
Countries
China
Outcome results
None listed