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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Assigned Interventions | Experimental | 1）Treatment will begin approximately 3 months post-transplant. The study duration will be 1 year with treatment cycles every 3 months, totaling 4 cycles.
|
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maintenance Therapy with Selinexor and Azacitidine | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease relapse | 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. | 1 year after transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Non-relapse mortality (NRM) | 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. | 1 year after transplantation |
| Overall survival (OS) |
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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).
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| Name | Affiliation | Role |
|---|---|---|
| Dai-hong Liu, Dr. | Chinese PLA General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese PLA General Hospital | Beijing | Beijing Municipality | 100853 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35816664 | Background | Mishra A, Tamari R, DeZern AE, Byrne MT, Gooptu M, Chen YB, Deeg HJ, Sallman D, Gallacher P, Wennborg A, Hickman DK, Attar EC, Fernandez HF. Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2022 Dec 1;40(34):3985-3993. doi: 10.1200/JCO.22.00181. Epub 2022 Jul 11. | |
| 34551341 |
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Data contain sensitive personal health information
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D008283 | Maintenance |
| C585161 | selinexor |
| D001374 | Azacitidine |
| ID | Term |
|---|---|
| D005159 | Health Care Facilities Workforce and Services |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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|
The time from transplantation to death of any cause or the last follow-up day. |
| 1 year after transplantation |
| Progress-free survival (PFS) | The time from the date of transplantation to the recurrence of leukemia or death for any reason. | 1 year after transplantation |
| Drug-related adverse events | All adverse events with a causal relationship to the study intervention (Selinexor + Azacitidine), assessed by investigators according to CTCAE v5.0 criteria. | 1 month after the last maintenance treatment ends |
| Measurable Residual Disease (MRD) in bone marrow | Quantitative assessment of residual leukemic cells using: FCM-MRD and TP53 mutation NGS testing | 1 year after transplantation |
| Background |
| Bewersdorf JP, Allen C, Mirza AS, Grimshaw AA, Giri S, Podoltsev NA, Gowda L, Cho C, Tallman MS, Zeidan AM, Stahl M. Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation-A Systematic Review and Meta-Analysis. Transplant Cell Ther. 2021 Dec;27(12):997.e1-997.e11. doi: 10.1016/j.jtct.2021.09.005. Epub 2021 Sep 20. |
| 38768424 | Background | Santini V, Stahl M, Sallman DA. TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates. Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e432650. doi: 10.1200/EDBK_432650. |
| 36902450 | Background | Zavras PD, Sinanidis I, Tsakiroglou P, Karantanos T. Understanding the Continuum between High-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia. Int J Mol Sci. 2023 Mar 6;24(5):5018. doi: 10.3390/ijms24055018. |
| 37036626 | Background | Najima Y. Overcoming relapse: prophylactic or pre-emptive use of azacitidine or FLT3 inhibitors after allogeneic transplantation for AML or MDS. Int J Hematol. 2023 Aug;118(2):169-182. doi: 10.1007/s12185-023-03596-w. Epub 2023 Apr 10. |
| 37189770 | Background | Rahme R, Braun T, Manfredi JJ, Fenaux P. TP53 Alterations in Myelodysplastic Syndromes and Acute Myeloid Leukemia. Biomedicines. 2023 Apr 11;11(4):1152. doi: 10.3390/biomedicines11041152. |
| 38024632 | Background | Patel SA, Cerny J, Gerber WK, Ramanathan M, Ediriwickrema A, Tanenbaum B, Hutchinson L, Meng X, Flahive J, Barton B, Gillis-Smith AJ, Suzuki S, Khedr S, Selove W, Higgins AW, Miron PM, Simin K, Woda B, Gerber JM. Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions. EJHaem. 2023 Sep 11;4(4):1059-1070. doi: 10.1002/jha2.791. eCollection 2023 Nov. |
| 36966300 | Background | Bhansali RS, Pratz KW, Lai C. Recent advances in targeted therapies in acute myeloid leukemia. J Hematol Oncol. 2023 Mar 25;16(1):29. doi: 10.1186/s13045-023-01424-6. |
| 38096805 | Background | Nawas MT, Kosuri S. Utility or futility? A contemporary approach to allogeneic hematopoietic cell transplantation for TP53-mutated MDS/AML. Blood Adv. 2024 Feb 13;8(3):553-561. doi: 10.1182/bloodadvances.2023010417. |
| 40011351 | Background | Masuda Y, Sadato D, Toya T, Hosoda Y, Hirama C, Shimizu H, Najima Y, Harada H, Harada Y, Doki N. Transplantation outcomes of TP53-mutant AML and MDS: a single transplantation center experience of 63 patients. Int J Hematol. 2025 Jun;121(6):820-832. doi: 10.1007/s12185-025-03951-z. Epub 2025 Feb 26. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |