Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results

NCT05736978 | Recruiting Phase 2

• 1 other identifier: AVS
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

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.

Conditions

AML; MRD

Keywords

untreated AML; MRD results; selinexor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Composite Complete Remission

  From the study start up to death (up to approximately 2 years; )

Secondary Outcomes (4)

• 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; )

Study Arms (1)

Treatment regimen based on C1D14 MRD

EXPERIMENTAL

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; Drug: Venetoclax; Drug: Selinexor

Interventions

Azacitidine DRUG

75mg/m2 d1-7

Treatment regimen based on C1D14 MRD

Venetoclax DRUG

d1 100mg, d2 200mg, d3-28 400mg

Also known as: ABT-199

Treatment regimen based on C1D14 MRD

Selinexor DRUG

if MRD positive in C1D14, selinexor 60mg D15, D22

Also known as: XPO1 inhibitor

Treatment regimen based on C1D14 MRD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Tong Ren Hospital: lead

Study Sites (4)

Beizhan Hospital

Shanghai, China

NOT YET RECRUITING

Pla Navy Feature Medical Center

Shanghai, China

NOT YET RECRUITING

Shanghai Ruijin Hospital

Shanghai, China

NOT YET RECRUITING

Shanghai Tong Ren hospital

Shanghai, China

RECRUITING

MeSH Terms

Interventions

Azacitidine; venetoclax; selinexor

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Ligen Liu, MD

CONTACT

18017337037; liuligen@shsmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director

Study Record Dates

• First Submitted: February 12, 2023
• First Posted: February 21, 2023
• Study Start: March 31, 2023
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 15, 2027
• Last Updated: March 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)