Clinical trial · Interventional
Maintenance Therapy With Selinexor and Azacitidine in TP53 Mutant AML/MDS After Transplantation
A Single-Arm, Open-Label Phase I Clinical Study of Selinexor Combined With Azacitidine for Maintenance Therapy in TP53 Mutant AML/MDS Patients Post-Transplant
NCT07094464CI-TRIAL-00092819active not recruitingPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | — | UNRESOLVED | — |
| TP53-mutated MDS and AML | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Maintenance Therapy with Selinexor and Azacitidine | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Assigned Interventions
- description
- 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. 1. Selinexor: Single-arm phase I study with sequential dose escalation of Selinexor. Three dose levels will be tested in separate cohorts: * 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 2. Azacitidine: 35 mg/m² for 5 days. 2）Bone marrow morphology, characteristic gene mutation or fusion gene quantification, immunophenotyping, chimerism, or transplant-related FISH will be assessed before and after each treatment cycle, according to the follow-up schedule post-transplant. Patients with hematological relapse at any time will discontinue from the experimental group and receive an alternative treatment.
- interventionNames
- Drug: Maintenance Therapy with Selinexor and Azacitidine
Primary outcomes (1)
- measure
- Disease relapse
- timeFrame
- 1 year after transplantation
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 14 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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).
References
Publications (10)
- BACKGROUNDMishra 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. PMID 35816664
- BACKGROUNDBewersdorf 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. PMID 34551341
- BACKGROUNDSantini 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. PMID 38768424
- BACKGROUNDZavras 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. PMID 36902450
- BACKGROUNDNajima 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. PMID 37036626
- BACKGROUNDRahme 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. PMID 37189770
- 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.