TP53-mutated MDS and AMLPhase 1NCT07094464

Maintenance Therapy With Selinexor and Azacitidine in TP53 Mutant AML/MDS After Transplantation

A Phase 1 study testing Maintenance Therapy with Selinexor and Azacitidine in people with TP53-mutated MDS and AML and Allogeneic Hematopoietic Stem Cell Transplantation, run by Daihong Liu at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 14 to 75 years
Conditions the study is for: TP53-mutated MDS and AML, Allogeneic Hematopoietic Stem Cell Transplantation
What is being tested?: Maintenance Therapy with Selinexor and Azacitidine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteChina
Study dates: 1 Jun 2025to 30 Dec 2028
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 14 to 75 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

(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.
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.
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.

Who cannot join

(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.
Patients with psychiatric disorders or conditions preventing informed consent, unable to comply with treatment and assessment requirements.
Patients who underwent major surgery on important organs less than 6 weeks prior.
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.
Patients deemed unsuitable for this clinical trial by the investigator (e.g., poor compliance, substance abuse).

Trial locations and contacts

1 site in 1 country.

China1 site

Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853

Other trials in China

About this study

Official title: 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

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.

Read the 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.

Conditions: TP53-mutated MDS and AML, Allogeneic Hematopoietic Stem Cell Transplantation
Being tested: Maintenance Therapy with Selinexor and Azacitidine
Keywords: TP53 mutant myeloid tumors, allogeneic hematopoietic cell transplantation.
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Maintenance Therapy with Selinexor and AzacitidineDrug
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.
1. Azacitidine: 35 mg/m² for 5 days.

Study groups in NCT07094464
Study group	Role	What they receive
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. 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. Receives: Drug: Maintenance Therapy with Selinexor and Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 year after transplantation

Secondary outcomes (5)

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.
Measured: 1 year after transplantation
Overall survival (OS)
The time from transplantation to death of any cause or the last follow-up day.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 1 year after transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 202530 Dec 2028

First posted30 Jul 2025
Study start1 Jun 2025
Primary completion30 Jun 2027 (estimated)
Study completion30 Dec 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (10)Papers the sponsor has linked to this study.
Other trials for TP53-mutated MDS and AMLStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07094464
Sponsor's protocol ID: S2025-055-01
Status last verified: Jul 2025
First submitted: 1 Jun 2025
Last updated: 30 Jul 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Data contain sensitive personal health information

Publications

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.
PubMed 35816664
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.
PubMed 34551341
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.
PubMed 38768424
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.
PubMed 36902450
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.
PubMed 37036626
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.
PubMed 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.
PubMed 38024632
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.
PubMed 36966300
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.
PubMed 38096805
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.
PubMed 40011351