Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results

Phase 2

Recruiting

• Conditions: MRD; AML
• Interventions: Drug: Azacitidine; Drug: Venetoclax; Drug: Selinexor

• Registration Number: NCT05736978
• Lead Sponsor: Shanghai Tong Ren Hospital

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 based on MRD results on day 14 of the first cycle.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-02-12
• Study First Submitted QC: 2023-02-12
• Study First Posted: 2023-02-21
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-13
• Last Update Posted: 2023-03-15
• Study Start: 2023-03-31
• Primary Completion: 2025-03-01
• Study Completion: 2027-03-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 58

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment regimen based on C1D14 MRD	Venetoclax	Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy will be given azacitidine 75mg/m2, d1-7 and venetoclax 100mg on day 1 and 200mg on day 2, 400mg on day 3-28. 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.
Treatment regimen based on C1D14 MRD	Selinexor	Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy will be given azacitidine 75mg/m2, d1-7 and venetoclax 100mg on day 1 and 200mg on day 2, 400mg on day 3-28. 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.
Treatment regimen based on C1D14 MRD	Azacitidine	Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy will be given azacitidine 75mg/m2, d1-7 and venetoclax 100mg on day 1 and 200mg on day 2, 400mg on day 3-28. 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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Composite Complete Remission	From the study start up to death (up to approximately 2 years; )

Secondary Outcome Measures

Name	Time	Method
overall survival (OS)	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; )
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; )

Trial Locations

Locations (4)

Pla Navy Feature Medical Center; 🇨🇳 Shanghai, China

Shanghai Ruijin Hospital; 🇨🇳 Shanghai, China

Shanghai Tong Ren hospital; 🇨🇳 Shanghai, China

Beizhan Hospital; 🇨🇳 Shanghai, China