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

Sponsor

Shanghai Tong Ren Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05736978

Collaborator

(none)

Enrollment

Locations

Arm

48.5

Anticipated Duration (Months)

14.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
AML MRD	Drug: Azacitidine Drug: Venetoclax Drug: Selinexor	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

58 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 15, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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; )]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Beizhan Hospital	Shanghai	China
2	Pla Navy Feature Medical Center	Shanghai	China
3	Shanghai Ruijin Hospital	Shanghai	China
4	Shanghai Tong Ren hospital	Shanghai	China