AML, Adult
Conditions
Keywords
selinexor, untreated AML, azacitidine, venetoclax
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.
Interventions
DRUGSelinexor
Selinexor 60mg, PO d3,10,17
DRUGAzacitidine
Azacitidine 75mg/m2, IV d1-3, 8-9, 15-16
DRUGVenetoclax
Venetoclax 100mg PO on day 1 and 200mg on day 2, 400mg on day 3-14
Sponsors
Shanghai Tong Ren Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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; ) |
Countries
China
Contacts
Primary ContactLigen Liu, MD
Outcome results
None listed