Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results

AML Clinical Trial

— AVS  

Official title:

Clinical Efficacy and Safety of Adaptive Treatment of Acute Myeloid Leukemia (AML) Based on D14 MRD results-a Multicenter, Single-arm, Prospective Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05736978
• Other study ID #: AVS
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2023
• Est. completion date: March 15, 2027

Study information

• Verified date: March 2023
• Source: Shanghai Tong Ren Hospital
• Contact: Ligen Liu, MD
• Phone: 18017337037
• Email: liuligen[@]shsmu.edu.cn
• 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 based on MRD results on day 14 of the first cycle.

Description:

Azacitidine and Venetoclax will be given at the approved dose regimen for 75mg/m2, d1-7(azacitidine) and 100mg on day 1 and 200mg on day 2, 400mg on day 3-28 (venetoclax), 28 days per cycle. Based on MRD results on C1D14, MRD negative patients will go on azacitidine and venetoclax regimen and for patients with MRD positive, selinexor 60mg on D15 and D22 will be added. 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: March 15, 2027
• Est. primary completion date: March 1, 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 .

• 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
• Leukemia, Myeloid, Acute
• MRD

Intervention

Drug:
• Azacitidine
75mg/m2 d1-7
• Venetoclax
d1 100mg, d2 200mg, d3-28 400mg
• Selinexor
if MRD positive in C1D14, selinexor 60mg D15, D22

Locations

Country	Name	City	State
China	Beizhan Hospital	Shanghai
China	Pla Navy Feature Medical Center	Shanghai
China	Shanghai Ruijin Hospital	Shanghai
China	Shanghai Tong Ren hospital	Shanghai

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		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; )