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

NCT07094464 | Active Not Recruiting Phase 1

• 1 other identifier: S2025-055-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

TP53-mutated MDS and AML; Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

TP53 mutant myeloid tumors; allogeneic hematopoietic cell transplantation.

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Non-relapse mortality (NRM)

  1 year after transplantation

• Overall survival (OS)

  1 year after transplantation

• Progress-free survival (PFS)

  1 year after transplantation

• Drug-related adverse events

  1 month after the last maintenance treatment ends

• Measurable Residual Disease (MRD) in bone marrow

  1 year after transplantation

Study Arms (1)

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.

Drug: Maintenance Therapy with Selinexor and Azacitidine

Interventions

Maintenance Therapy with Selinexor and Azacitidine DRUG

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.

Assigned Interventions

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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).

Sponsors & Collaborators

• Daihong Liu: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Related Publications (10)

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  PMID: 9533376 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.

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  PMID: 10002503 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.

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  PMID: 10835231 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.

  PMID: 40011351 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Maintenance; selinexor; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Health Care Facilities Workforce and Services; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Dai-hong Liu, Dr.

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: June 1, 2025
• First Posted: July 30, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)