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

Sponsor

Shanghai Tong Ren Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05736965

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

14.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
AML, Adult	Drug: Selinexor Drug: Azacitidine Drug: Venetoclax	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

58 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 30, 2025

Anticipated Study Completion Date :

Apr 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAV arm 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 Selinexor 60mg, PO d3,10,17 Other Names: xpo1 inhibitor 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 Other Names: ABT199

Arm

Intervention/Treatment

Experimental: SAV arm

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

Selinexor 60mg, PO d3,10,17

Other Names:

xpo1 inhibitor

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

Other Names:

ABT199

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Composite Complete Remission [From the study start up to death (up to approximately 2 years; )]
composite complete remission(CR , CRh, CRi) was calculated based on ELN2022 criteria.

Secondary Outcome Measures

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; )]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country
1	The First Affiliated Hospital of Zhejiang University	Hangzhou	China
2	Shanghai Ruijin Hospital	Shanghai	China
3	Shanghai Tong Ren hospital	Shanghai	China
4	Tongji Hospital Affiliated to Huazhong University of Science and Technology	Wuhan	China