Clinical trial NCT05736965: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: AML, Adult
Keywords: selinexor
untreated AML
azacitidine
venetoclax
Lead sponsor: Shanghai Tong Ren Hospital
Sponsor class: OTHER
First posted: 2023-02-21
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Percentage of Participants With Composite Complete Remission
timeFrame: From the study start up to death (up to approximately 2 years; )
Secondary outcomes:
measure: overall survival (OS)
timeFrame: From the study start up to death (up to approximately 4 years; )
measure: Overall response rate(ORR)
timeFrame: From the study start up to death (up to approximately 4 years; )
measure: percentage of patients who achieved MRD negativity
timeFrame: From the study start up to death (up to approximately 4 years; )
measure: Recurrence Free Survival(RFS)
timeFrame: From the study start up to death (up to approximately 4 years; )
Other outcomes:
Locations:
city: Ch'ang-ch'un
country: China
facility: Jilin University China Japan Union Hospital
city: Changzhou
country: China
facility: Changzhou Municipal No.1 People's Hospital
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Ha'erbin
country: China
facility: Harbin Institute of Hematology and Oncology
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Jiaxing
country: China
facility: the first hospital of Jiaxing affiliated hospital of Jiaxing University
city: Lanzhou
country: China
facility: Gansu Provincial People's Hospital
city: Lanzhou
country: China
facility: Lanzhou University NO.2 Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Huspital
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Tong Ren hospital
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shijia Zhuang
country: China
facility: The First Hospital of Hebei Medical University
city: Shijia Zhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Wuhu
country: China
facility: the Second Affiliated Hospital of Wannan Medical College
city: Xi'an
country: China
facility: Xi'an International Medical Center
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
city: Yixing
country: China
facility: Yixing People's Hospital
city: Ürümqi
country: China
facility: First Affiliated Hospital of Xinjiang Medical University
Study officials:
References: