Clinical trial NCT06449482: Selinexor、Venetoclax and Azactidine in the Treatment of ND AML Patients Who Are Not Eligible for Intense Chemotherapy
Official title: An Exploratory Clinical Study of Selinexor Combined With Venetoclax and Azactidine in the Treatment of Acute Myeloid Leukemia Patients Who Are Not Eligible for Intense Chemotherapy Regimen at Initial Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia, Adult
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-06-10
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: selinexor venetoclax and azacitidine
Primary purpose: TREATMENT

Brief summary: This study is a single arm open exploratory clinical trial to evaluate the efficacy and safety of selinexor combined with venetoclax and azacitidine. This study will be divided into two stages: dose increasing stage and dose expanding stage. In the dose-increasing stage, the study induction therapy was designed using a 3+3 design. The induction therapy and consolidation therapy of the subjects will be administered at RP2D doses.

During this study period, there were a total of 4 cycles. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy.

In addition, if the subject does not achieve remission (CR/Cr or PR) after 2 cycles of consolidation treatment (at the end of the 4th course), the study will be terminated by the subject, and the clinical doctor will choose the subsequent treatment for the subject based on clinical experience.

Detailed description: This study is a single arm open exploratory clinical trial to evaluate the efficacy and safety of selinexor combined with venetoclax and azacitidine. This study will be divided into two stages: dose increasing stage and dose expanding stage. In the dose-increasing stage, the study induction therapy was designed using a 3+3 design. In this stage, three dosage groups were set up, namely selinexor 60mg QW, 40mg BIW, or 60mg BIW, in combination with venetoclax 100mg d1 200mg d2 400mg d3-28, orally once a day, and azacitidine 75mg/m2, d1-7, subcutaneously. The regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data.

The methods of venetoclax and azacitidine remain unchanged during consolidation therapy. Before RP2D is determined, the dosage of selinexor is determined by the researchers based on individual subject tolerance. After RP2D is determined, the study enters the second stage of dose expansion. The induction therapy and consolidation therapy of the subjects will be administered at RP2D doses.

During this study period, there were a total of 4 cycles. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy. In addition, if the subject does not achieve remission (CR/Cr or PR) after 2 cycles of consolidation treatment (at the end of the 4th course), the study will be terminated by the subject, and the clinical doctor will choose the subsequent treatment for the subject based on clinical experience.

The subjects will participate in the screening period, treatment period, and follow-up period. The screening period lasts for a maximum of 28 days before medication. The treatment period lasts from the first day of the first cycle to the end of the study treatment. The follow-up period starts after the end of treatment and lasts for at least 12 months.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed AML patients diagnosed according to WHO standards who are not suitable for the standard induction treatment regimen of cytarabine combined with anthracycline drugs due to age or comorbidities.
2. Age ≥ 75 years old, ECOG score 0-2 points; The patient's age range is 18-75 years old, with an ECOG score of 0-3.
3. Liver function meets the following criteria: total bilirubin\<3 × Upper limit of normal range (ULN) (\<75 years old), total bilirubin\<1.5 × ULN (≥ 75 years old), AST\<3 × ULN and ALT\<3 × ULN.
4. Renal function meets the following criteria: creatinine clearance rate ≥ 30 mL/min (Cockroft-Gault formula).
5. Expected survival time greater than 6 months

Exclusion Criteria:

1. patient who has received BCL2 inhibitors, demethylation drugs, chemotherapy, CAR-T therapy, or other experimental therapies.
2. History of myeloproliferative tumors (MPN).
3. Cytogenetic low risk, such as t (8; 21), inv (16), t (16; 16) or t (15; 17).
4. Acute promyelocytic leukemia.
5. AML central nervous system (CNS) involvement.
6. Pregnancy or lactation period.
7. I underwent major surgery within 4 weeks before the first study medication.
8. Subjects with unstable or active cardiovascular diseases who meet any of the following criteria:
9. Symptomatic myocardial ischemia;

Primary outcomes:
measure: RP2D of selinexor in this study
timeFrame: 1 year
Secondary outcomes:
measure: MRD negative rate
timeFrame: up to 16 weeks
measure: Compound complete response rate
timeFrame: up to 16 weeks
measure: The time to compound complete response
timeFrame: up to 16 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
References: