The Efficacy and Safety of Selinisole Combined With Azacitidine and Venetoclax in the Treatment of Newly Diagnosed High-risk Myeloid Tumors With TP53 Mutations

NCT07632170 | Not Yet Recruiting

• 1 other identifier: Selinexor+AZA+/-VEN
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with high-risk myeloid tumors accompanied by TP53 mutations have a poor survival prognosis, and there are still many unmet treatment needs. The current treatment regimens have many limitations. Selinisol, as a novel export protein inhibitor, has good anti-tumor activity. The current preclinical and preliminary clinical research results abroad suggest its effectiveness and safety. This study aims to evaluate the efficacy and safety of AZA combined with selinisole (with or without venetoclax) in the treatment of patients with high-risk myeloid tumors with TP53 mutations through a multicenter, prospective clinical study.

Conditions

Myeloid Tumors

Keywords

Myeloid Tumors; TP53; Selinexor; Venetoclax; Azacitidine

Outcome Measures

Primary Outcomes (2)

• 3 and 6 months overall response rate (ORR)

  The overall response rate (ORR) after the completion of 3 and 6 months. The overall response rate (ORR) is defined as the ratio of patients achieving complete response (CR) plus partial response (PR)

  3 and 6 months

• 3 and 6 months complete response rate (CRR)

  The complete response rate (CRR) after the completion of 3 and 6 months.

  3 and 6 months

Secondary Outcomes (4)

• Progression-free survival (PFS);

  6 months

• Overall survival (OS);

  6 months

• The incidence of cumulative infection and significant bleeding;

  6 months

• Incidence of adverse reaction events.

  6 months

Study Arms (1)

Azacitidine +Selinexor ± venetoclax

EXPERIMENTAL

Azacitidine +Selinexor ± venetoclax were administered (Selinexor: 60mg/ week, qw\*4 weeks; azacitidine: 100mg/m2\*d1-d7; venetoclax, 100mg d1-14). The specific medication duration can be adjusted by the researcher based on the patient's specific condition. A time window of 14 to 28 days is allowed. Each treatment cycle lasts for 30 days until disease progression or the occurrence of intolerable toxicity, whichever comes first.

Drug: Selinexor

Interventions

Selinexor DRUG

Azacitidine +Selinexor ± venetoclax were administered (Selinexor: 60mg/ week, qw\*4 weeks; azacitidine: 100mg/m2\*d1-d7; venetoclax, 100mg d1-14). The specific medication duration can be adjusted by the researcher based on the patient's specific condition. A time window of 14 to 28 days is allowed. Each treatment cycle lasts for 30 days until disease progression or the occurrence of intolerable toxicity, whichever comes first.

Also known as: Azacitidine, venetoclax

Azacitidine +Selinexor ± venetoclax

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old; Gender is not limited.
• The presence of TP53 mutations (According to the 5th Edition of the WHO Classification of hematopoietic and lymphoid tumors and the International Consensus Classification (ICC 2022), the definition of myeloid tumors with TP53 mutations is: pathogenic/potentially pathogenic variations of the TP53 gene are detected through molecular technologies such as next-generation sequencing (NGS), and any of the following conditions are met: The frequency of variant alleles (VAF) is ≥10%, or there are multiple TP53 mutations (≥2 mutations), or both TP53 mutations and 17p deletion (del(17p)) are present.
• MDS (IPSS-R/IPSS-M at high risk or above; or complex karyotype/alone -5/-5q, -7/-7q, i (17q), inv (3)/t(3;3); Or bone marrow blasts ≥10%; 3.2 AML (bone marrow/peripheral blood blasts ≥20%; and high-risk cytogenetic or molecular abnormalities exist); 3.3 MPN (High risk score above threat; or presence of any one of ASXL1, SRSF2, EZH2, IDH1/2, or U2AF1 gene mutations; or bone marrow blasts ≥10%); 3.4 MDS/MPN (IPSS-R high-risk or above; or bone marrow blast granulocytes ≥10%).
• Voluntarily join this study, sign the informed consent form with good compliance, and be willing to cooperate with regular follow-ups for efficacy evaluation and side effect monitoring.
• Before treatment, the patient's total bilirubin (TBIL) was less than 1.5 times the upper limit of the normal value (ULN), and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were less than 3 times the ULN.
• ECOG score ≤2 points.

You may not qualify if:

• Patients who have transplant plans within three months;
• All laboratory or clinical records of HIV infection, previous clinical history of hepatitis C, previous hepatitis B infection, or evidence of active hepatitis during screening. Laboratory tests during the screening period suggest hepatitis C infection or hepatitis B infection. (Defined as a positive HBsAg test. Additionally, if the HBsAg test is negative but HBcAb is positive, regardless of the HBsAb status, HBV DNA testing is required. If it is positive, the subject should be excluded.)
• Suffering from mental disorders or other conditions and unable to cooperate with the requirements of research, treatment and monitoring;
• Pregnant patients or those who cannot take appropriate contraceptive measures during the treatment period;
• Those suspected of being allergic to the experimental drug or any of its excipients;
• Active heart disease is defined as one or more of the following:
• ① A history of uncontrolled or symptomatic angina pectoris;
• ② Myocardial infarction less than 6 months from the time of enrollment in the study;
• ③ There is a history of arrhythmia that requires drug treatment or has severe clinical symptoms;
• ④ Uncontrolled or symptomatic congestive heart failure (NYHA grade 2)
• ⑤ The ejection fraction is lower than the lower limit of the normal range.
• Patients who the researchers consider unsuitable to participate in this trial, such as those whose safety or compliance with the study procedures may be affected by any other medical, social or psychological factors.

Sponsors & Collaborators

• Bing Han: lead

Study Sites (1)

Peking union medical college hospital

Beijing, Shuangfuyuan, NO I., China

Location

MeSH Terms

Interventions

selinexor; Azacitidine; venetoclax

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Peking Union Medical College Hospital

Study Record Dates

• First Submitted: September 28, 2025
• First Posted: June 8, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 10 years
• Access Criteria: email request

Locations

CN (1)