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

Official title

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

Overview

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

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.

Interventions

• Drug Selinexor
  Selinexor 60mg, PO d3,10,17
• Drug Azacitidine
  Azacitidine 75mg/m2, IV d1-3, 8-9, 15-16
• Drug Venetoclax
  Venetoclax 100mg PO on day 1 and 200mg on day 2, 400mg on day 3-14

Primary outcome measures

• Percentage of Participants With Composite Complete Remission [Time frame: From the study start up to death (up to approximately 2 years; )]

Secondary outcome measures (4)

• overall survival (OS) [Time frame: From the study start up to death (up to approximately 4 years; )]
• Overall response rate(ORR) [Time frame: From the study start up to death (up to approximately 4 years; )]
• percentage of patients who achieved MRD negativity [Time frame: From the study start up to death (up to approximately 4 years; )]
• Recurrence Free Survival(RFS) [Time frame: From the study start up to death (up to approximately 4 years; )]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 19 centers

• Changzhou Municipal No.1 People's Hospital — Changzhou
• Sichuan Provincial People's Hospital — Chengdu
• Jilin University China Japan Union Hospital — Ch’ang-ch’un
• Harbin Institute of Hematology and Oncology — Ha’erbin
• Anhui Provincial Hospital — Hefei
• the first hospital of Jiaxing affiliated hospital of Jiaxing University — Jiaxing
• Gansu Provincial People's Hospital — Lanzhou
• Lanzhou University NO.2 Hospital — Lanzhou
• … and 11 more centers

Identifiers

NCT: NCT05736965 · SAV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗