Clinical trial NCT06900088: Selinexor Combined With Azacitidine Therapy in High-Risk Myeloid Neoplasms Patients
Official title: Efficacy and Safety of Selinexor Combined With Azacitidine as Maintenance Therapy in High-Risk Myeloid Neoplasms Patients Post-Transplantation: A Single-Center, Single-Arm, Explorato
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Efficacy and Safety of Selinexor Combined with Azacitidine as Maintenance Therapy in High-Risk Myeloid Neoplasms Patients Post-Transplantation: A Single-Center, Single-Arm, Exploratory Study

Detailed description: Treatment period: From the time of transplantation, after screening by inclusion and exclusion criteria, patients who meet the criteria are enrolled and given maintenance therapy with Selinexor in combination with azacitidine (Selinexor: 40 mg/weekly, administered on D1; azacitidine: 50 mg/m2\*5d; every 28 days for a cycle of treatment, for at least one year of medication, or until progression of the disease, or until the development of intolerable toxicity, whichever comes first)

Eligibility criteria: Inclusion criteria:

with pre-transplant MRD-positive AML, i.e., patients who meet one of the following criteria:

1. Age≥ 16 years old; any gender;
2. High-risk MDS (IPSS-R or/and IPSS-M high-risk and above);
3. High relapse risk AML, including relapsed refractory AML and patients with pre-transplant MRD-positive AML, i.e., patients who meet one of the following criteria:

(1)Refractory AML is defined as meeting one of the following conditions

1. Primary cases that have failed to respond to 2 courses of standard regimen chemotherapy;
2. CR was followed by consolidation and intensive treatment with no recurrence within 12 months;
3. It recurred 12 months later, but conventional chemotherapy was ineffective;
4. 2 or more relapses;
5. Extramedullary leukemia persists. (2)Relapsed AML i.e., re-initialization of leukemic cells in the peripheral blood after complete remission (CR) or bone marrow primitive cells \>0.050 (except for other reasons such as bone marrow reconstitution after consolidation chemotherapy) or extramedullary infiltration of leukemic cells.

(3)Positive pre-transplant MRD, i.e., one of the following conditions is met:

1. Proportion of abnormal myeloid cells \>0.01% by pre-transplant flow assay;
2. Positive pre-transplantation molecular biology-related tests. (4)AML with poor prognosis (according to the Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Myeloid Leukemia (Non-Acute Promyelocytic Leukemia) 2023 Edition) 4.Meets WHO diagnostic criteria for staging CMML; 5.MDS or CMML transforms AML.

Exclusion criteria:

Patients with any of the following are not eligible for enrollment in this study:

1. Patients who relapsed within 3 months of transplantation or during maintenance therapy, including hematologic, molecular genetic, cytogenetic relapses, and extramedullary relapses.
2. Known positive serology for HIV or active hepatitis B virus (HBV) and hepatitis C virus (HCV);
3. Requirements for mental illness or other conditions that preclude cooperation with study treatment and monitoring;
4. Patients who are pregnant or who are unable to use appropriate contraception during treatment;
5. Suspected hypersensitivity to the experimental drug or any of its excipients;
6. Active heart disease, defined as one or more of the following:

（1）History of uncontrolled or symptomatic angina; （2）Myocardial infarction less than 6 months from study entry; （3）History of tardive dyskinesia requiring medication or clinically significant symptoms; （4）Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2) （5）Ejection fraction is below the lower limit of the normal range. 7. Those deemed unsuitable for enrollment by the investigator.

Primary outcomes:
measure: 2-year recurrence free survival rate (RFS)
timeFrame: 2 years
Secondary outcomes:
measure: 2-year non-relapse mortality rate (NRM)
timeFrame: 2 years
measure: 2-year survival rate (OS)
timeFrame: 2 years
measure: Median overall survival (OS)
timeFrame: 2 years
measure: Cumulative incidence of acute graft-versus-host disease (GVHD)
timeFrame: 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
Study officials:
References: