Acute myeloid leukemia
Conditions
Interventions
Induction therapy group:Selinisol: Oral administration of 40mg BIW, d1, d4, d8, d11, d15, d18 (use for 3 weeks, then stop for 1 week)
Venetoclax: Oral administration 100mg on day 1, 200mg on day 2, 40
Maintain therapy group:Selinexor: 40 mg orally twice weekly (BIW) for 3 weeks followed by a 1-week break.
Venetoclax: 400 mg orally once daily (QD) on days 1–28.
Sponsors
The First Affiliated Hospital of Nanchang University
Eligibility
Sex/Gender
All
Age
60 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Newly diagnosed acute myeloid leukemia and unfit for intensive induction chemotherapy, or myelodysplastic syndrome with International Prognostic Scoring System (IPSS) >4.5. According to the Ferrara consensus criteria, a patient is considered unfit if at least one of the following criteria is met: (1) Advanced age: >75 years. (2) Severe cardiac comorbidity: Congestive heart failure or history of myocardial disease with previous ejection fraction (EF) 60 years and currently receiving dialysis, or uncontrolled renal tumor. (5) Severe hepatic comorbidity: Child-Pugh class B or C cirrhosis, or age >=60 years with liver disease causing a marked elevation of transaminases (>3 times the upper limit of normal), or any cholangiocarcinoma, or uncontrolled liver cancer or acute viral hepatitis. (6) Active infection unresponsive to anti-infective therapy. (7) Cognitive impairment: Currently suffering from a psychiatric disorder requiring hospitalization in a psychiatric hospital or custodial facility, or enhanced outpatient management, or a dependent cognitive state not controlled by the caregiver (diagnosed by a specialist). (8) Poor performance status (ECOG score): ECOG performance status score >=3 unrelated to leukemia. (9) Other comorbidities judged by the physician as making the patient unsuitable for chemotherapy. 2. Age >60 years. 3. ECOG performance status 0-3. 4. Laboratory tests meeting the following criteria: Serum creatinine 3 months. 6. Female subjects of childbearing potential must meet both of the following criteria: (1) Agree to use effective contraceptive measures from the time of signing the informed consent form, during the study drug period, and for 3 months after the last dose of study drug. (2) Have a negative serum pregnancy test at screening. Note: A woman of childbearing potential is defined as any female who has started menstruation, is not postmenopausal, and has not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as amenorrhea for more than 12 consecutive months for no specific reason. Women using oral contraceptives or mechanical contraceptive methods such as intrauterine devices should be considered as having childbearing potential. 7. Male subjects (including those who have undergone vasectomy) must agree to use a condom during sexual intercourse with a woman of childbearing potential and have no plan to impregnate a female partner from the time of signing the informed consent form, during the study drug period, and for 3 months after the last dose of study drug. 8. The patient or their legal guardian must be able to understand and willing to participate in this study and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia. 2. Patients with chronic myeloid leukemia in blast crisis. 3. Patients with leukemia involving the central nervous system. 4. Clinically significant major cardiovascular disease: (1) Cardiac dysfunction, New York Heart Association (NYHA) class II or higher. (2) Ischemic heart disease such as myocardial infarction or unstable angina pectoris, supraventricular arrhythmia or ventricular arrhythmia of clinical significance. 5. Patients who, in the investigator's judgment, are allergic, resistant, or intolerant to any drug in the planned combination regimen. 6. Active bleeding from visceral organs. 7. Active infection that is not effectively controlled by medication within 1 week before the first study drug administration. 8. History of stroke or intracranial hemorrhage within 3 months; or active gastrointestinal bleeding of grade 3 or higher. 9. Patients with severe organ dysfunction. 10. With another concurrent cancer. 11. Patients previously treated with a BCL2 inhibitor or an XPO1 inhibitor. 12. Patients with active hepatitis B (HBV) or hepatitis C (HCV) infection. Note: Subjects who are HBsAg (HBV surface antigen)-negative and HBcAb-positive may be enrolled if HBV-DNA is undetectable; subjects who are HCV antibody-positive are excluded if HCV-RNA is undetectable. 13. Active psychiatric disease, alcoholism, drug abuse, or substance abuse. 14. Pregnant or breastfeeding women. 15. Other patients deemed unsuitable for enrollment by the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate(ORR);Compound complete remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DOR);Progression-free survival (PFS);overall survival (OS);Early mortality rate;minimal residual diseas(MRD); | — |
Countries
China
Contacts
Public ContactLi Fei, Hu Jinfang
The First Affiliated Hospital of Nanchang University
Outcome results
None listed