A Study of Selinexor in Combination With Azacitidine and Venetoclax (SAV Regimen) in Treatment Naïve Participants With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia.

Detailed Description
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This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia. Selinexor will be given orally at 60mg, d3,10,17 Azacitidine will be given at 75mg/m2, d1-3, 8-9, 15-16 Venetoclax will be given orally at 100mg on day 1 and 200mg on day 2, 400mg on day 3-14 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive treatment until disease progression or unacceptable toxic effects.

Official Title
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Clinical Efficacy and Safety of Selinexol Combined With Azacitidine and Venetoclax (SAV Regimen) in the Treatment of Acute Myeloid Leukemia (AML)-a Multi-center, Single-arm, Prospective Clinical Study

Conditions
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AML, Adult

Intervention / Treatment
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* Drug: Selinexor
* Drug: Azacitidine
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Known and written informed consent voluntarily Age ≥ 18 years Newly diagnosed AML patients (per WHO 2022 classification criteria for AML diagnosis), who are not suitable for intensive chemotherapy: ≥75 years or Aged 18 to 74 years with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or 3 or 4; Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; Creatinine clearance >= 30 mL/min to < 45 ml/min; Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy . patients who are suitable for intensive chemotherapy but refuse it Liver function meets the following criteria: aspartate aminotransferase (AST) ≤ 3.0×ULN*; alanine aminotransferase (ALT) ≤ 3.0×ULN*; Bilirubin≤1.5×ULN*; For subjects <75 years old, the bilirubin level can be ≤3.0×ULN; Unless due to leukemic organ involvement. Renal function meets the following criteria: creatinine clearance ≥ 30 mL/min (Cockroft-Gault formula) Life expectancy ≥ 4 weeks Exclusion Criteria: History of any malignancies prior to study entry with exception noted in the protocol. Participant has known HIV infection, active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) . Participant has known active central nervous system (CNS) involvement with AML. Must not have received prior anti-AML treatment except for hydroxyurea

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAV arm<br>Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects. | Drug: Selinexor<br>* Selinexor 60mg, PO d3,10,17<br>* Other names: xpo1 inhibitor;Drug: Azacitidine<br>* Azacitidine 75mg/m2, IV d1-3, 8-9, 15-16<br>Drug: Venetoclax<br>* Venetoclax 100mg PO on day 1 and 200mg on day 2, 400mg on day 3-14<br>* Other names: ABT199;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Composite Complete Remission | composite complete remission(CR , CRh, CRi) was calculated based on ELN2022 criteria. | From the study start up to death (up to approximately 2 years; ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) |  | From the study start up to death (up to approximately 4 years; ) | 
| Overall response rate(ORR) |  | From the study start up to death (up to approximately 4 years; ) | 
| percentage of patients who achieved MRD negativity |  | From the study start up to death (up to approximately 4 years; ) | 
| Recurrence Free Survival(RFS) |  | From the study start up to death (up to approximately 4 years; ) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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selinexor, untreated AML, azacitidine, venetoclax