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.
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.
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.
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;
Single group
Selinexor
DrugAzacitidine +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.
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 complete response rate (CRR)
The complete response rate (CRR) after the completion of 3 and 6 months.
Progression-free survival (PFS);
Overall survival (OS);
The incidence of cumulative infection and significant bleeding;
Incidence of adverse reaction events.
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Bing Han
Lead sponsor
Peking Union Medical College Hospital
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
