Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results (AVS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: AML; MRD
• Intervention / Treatment: Drug: Azacitidine; Drug: Venetoclax; Drug: Selinexor

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 Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ligen Liu, MD; Phone Number: 18017337037; Email: liuligen@shsmu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Tong Ren Hospital
    • Contact: Ligen Liu
  • Shanghai, China
    • Not yet recruiting
    • Shanghai Ruijin Hospital
    • Contact: Junmin Li
  • Shanghai, China
    • Not yet recruiting
    • Beizhan Hospital
    • Contact: Jie Hao
  • Shanghai, China
    • Not yet recruiting
    • Pla Navy Feature Medical Center
    • Contact: Rong Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment regimen based on C1D14 MRD; 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.

Drug: Azacitidine; 75mg/m2 d1-7; Drug: Venetoclax; d1 100mg, d2 200mg, d3-28 400mg; Other Names: ABT-199; Drug: Selinexor; if MRD positive in C1D14, selinexor 60mg D15, D22; Other Names: XPO1 inhibitor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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; )

Collaborators and Investigators

• Sponsor: Shanghai Tong Ren Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 31, 2023
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 15, 2027

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: February 12, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: selinexor; untreated AML; MRD results
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: AVS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No