Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results

NCT ID: NCT05736978

Last Updated: 2023-03-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2027-03-15

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.

Conditions

AML; MRD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

75mg/m2 d1-7

Venetoclax

Intervention Type: DRUG

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

Selinexor

Intervention Type: DRUG

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

Interventions

Azacitidine

75mg/m2 d1-7

Intervention Type: DRUG

Venetoclax

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

Intervention Type: DRUG

Selinexor

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

Intervention Type: DRUG

Other Intervention Names

ABT-199; XPO1 inhibitor

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Tong Ren Hospital

OTHER

Sponsor Role: lead

Responsible Party

Liu Ligen

director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beizhan Hospital

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Pla Navy Feature Medical Center

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Shanghai Ruijin Hospital

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Shanghai Tong Ren hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Ligen Liu, MD

Role: CONTACT

liuligen@shsmu.edu.cn

18017337037

Facility Contacts

Jie Hao

Role: primary

Rong Li

Role: primary

Junmin Li

Role: primary

Ligen Liu

Role: primary

Other Identifiers

AVS

Identifier Type: -

Identifier Source: org_study_id