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

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

Conditions: AML, Adult

Treatments: Drug: Azacitidine; Drug: Selinexor; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT05736965

SAV

Details and patient eligibility

About

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.

Full 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.

Enrollment: 58 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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58 participants in 1 patient group

SAV arm

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Azacitidine

Drug: Selinexor