Selinexor、Venetoclax and Azactidine in the Treatment of ND AML Patients Who Are Not Eligible for Intense Chemotherapy

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia, Adult
• Interventions: Drug: Selinexor; Drug: Venetoclax; Drug: Azacitidine

• Registration Number: NCT06449482
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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 c...

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...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2023-05-05
• Study First Submitted: 2023-06-13
• Status Verified: 2024-03
• Study First Submitted QC: 2024-06-03
• Last Update Submitted: 2024-06-03
• Study First Posted: 2024-06-10
• Last Update Posted: 2024-06-10
• Primary Completion: 2025-04-30
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
selinexor venetoclax Azacitidine	Venetoclax	In the dose-increasing stage, the subject induction therapy was designed using a 3+3 design. 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 medication regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data. During this study period, there were a total of 4 courses. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy.
selinexor venetoclax Azacitidine	Selinexor	In the dose-increasing stage, the subject induction therapy was designed using a 3+3 design. 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 medication regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data. During this study period, there were a total of 4 courses. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy.
selinexor venetoclax Azacitidine	Azacitidine	In the dose-increasing stage, the subject induction therapy was designed using a 3+3 design. 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 medication regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data. During this study period, there were a total of 4 courses. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy.

Primary Outcome Measures

Name	Time	Method
RP2D of selinexor in this study	1 year	from the first day to the last day of the cycle

Secondary Outcome Measures

Name	Time	Method
MRD negative rate	up to 16 weeks	MRD negative rate at the end of 2 cycles and 4 cycles of induction therapy
The time to compound complete response	up to 16 weeks	From first dose of treatment to first day response is documented by evaluation
Compound complete response rate	up to 16 weeks	From first dose of treatment to first day response is documented by evaluation

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, Tianjin, China