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

AML, Adult Clinical Trial

— SAV  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05736965
• Other study ID #: SAV
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2023
• Est. completion date: April 30, 2027

Study information

• Verified date: March 2023
• Source: Shanghai Tong Ren Hospital
• Contact: Ligen Liu, MD
• Phone: 18017337037
• Email: llg3532[@]shtrhospital.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: April 30, 2027
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• AML, Adult
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
China	Jilin University China Japan Union Hospital	Ch'ang-ch'un
China	Changzhou Municipal No.1 People's Hospital	Changzhou
China	Sichuan Provincial People's Hospital	Chengdu
China	Harbin Institute of Hematology and Oncology	Ha'erbin
China	Anhui Provincial Hospital	Hefei
China	the first hospital of Jiaxing affiliated hospital of Jiaxing University	Jiaxing
China	Gansu Provincial People's Hospital	Lanzhou
China	Lanzhou University NO.2 Hospital	Lanzhou
China	Ningbo Medical Center Lihuili Huspital	Ningbo
China	Shanghai Ruijin Hospital	Shanghai
China	Shanghai Tong Ren hospital	Shanghai
China	The First Hospital of China Medical University	Shenyang
China	The First Hospital of Hebei Medical University	Shijia Zhuang
China	The Second Hospital of Hebei Medical University	Shijia Zhuang
China	First Affiliated Hospital of Xinjiang Medical University	Ürümqi
China	the Second Affiliated Hospital of Wannan Medical College	Wuhu
China	Xi'an International Medical Center	Xi'an
China	Northern Jiangsu People's Hospital	Yangzhou
China	Yixing People's Hospital	Yixing

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Tong Ren Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	overall survival (OS)		From the study start up to death (up to approximately 4 years; )
Secondary	Overall response rate(ORR)		From the study start up to death (up to approximately 4 years; )
Secondary	percentage of patients who achieved MRD negativity		From the study start up to death (up to approximately 4 years; )
Secondary	Recurrence Free Survival(RFS)		From the study start up to death (up to approximately 4 years; )