MRD-positive AML Clinical Study

Institute of Hematology & Blood Diseases Hospital, China

Status: Enrolling

Conditions: AML, Adult

Treatments: Drug: Azacitidine; Drug: Venetoclax; Drug: Cytarabine; Drug: MTZ; Drug: Idarubicin; Drug: HHT; Drug: Daunorubicin; Drug: Avapritinib; Drug: Gilteritinib; Drug: Ivosidenib

Study type: Interventional

Funder types: Other

Identifiers

NCT07131059

IIT2024032

Details and patient eligibility

About

This clinical trial is a platform-type clinical study intended to investigate the efficacy and safety of MRD-positive acute myeloid leukemia patients after comprehensive treatment, which includes but is not limited to the following drugs and protocols: Chemotherapy, small molecule targeted drugs, demethylation drugs, liposome drugs and the combination of these drugs to form a combination of treatment regimen, the specific treatment regimen will be updated according to the results of this trial and the latest research progress at home and abroad.

Full description

Patients aged 14 years or older with diagnosed AML (non-M3) who have achieved complete remission in bone marrow morphology but are positive for minimal residual disease by flow cytometry or have the following genetic mutations that can be detected by PCR: NPM1 mutation, IDH1/2 mutation, DEK-NUP214 (DEK-CAN), RUNX1-RUNX1T1(AML 1-ETO), or CBFβ-MYH 11[4]. NGS can detect mutations such as FLT3.

For eligible patients, the treatment plan is selected by the doctor in charge according to the specific conditions of the patient. During the treatment, patients can have hematopoietic stem cell transplantation at any time.

This study compared relapse-free survival and overall survival of MRD-positive patients after effective and persistent MRD treatment, and based on the results, observed the efficacy and safety of different treatment regiments for MRD-positive AML patients.

Enrollment: 120 estimated patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• AML (non-M3) compliant with WHO (2016) standards;
• In morphological complete remission.
• Mrd-positive patients: including bone marrow flow cytometry, PCR quantification of NPM1 mutations, PCR quantification of fusion genes (RUNX 1-RUNX1T1, CBFB-MYH11 and DEK-NUP214), or NGS detection of FLT3 mutation positive.
• Age over 14 years old, male or female. Informed consent must be signed prior to the commencement of all specific study procedures, and for those 14 years of age and older, informed consent must be signed by the patient or an immediate family member. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient's immediate family.

Exclusion criteria

• Patients who intend to undergo hematopoietic stem cell transplantation within 4 weeks
• The diagnosis is APL
• Those who were not considered suitable for inclusion by the researchers.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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120 participants in 7 patient groups

With lDH1 gene mutation

Experimental group

Description:

Ivosidenib 500mg/d d1-28 ；Azacitidine 75mg/m2/d d1-7；Venetoclax400mg/d:d1-28

Treatment:

Drug: Ivosidenib

Drug: Venetoclax

FLT3 gene mutation

Experimental group

Description:

Gilteritinilb 120mg/d, d1 -28； Venetocax 400mg/d d1-28 400mg

Treatment:

Drug: Gilteritinib

Drug: Venetoclax

NPM1 mutation or IDH2 mutation

Experimental group

Description:

Azacitidine 75mg/m2/d d1-7；Venetoclax400mg/d d1-21 or Cytarabine 20mg/m2/d d1-10；Venetoclax 600mg/d d1-21

Treatment:

Drug: Venetoclax

c-kit mutation

Experimental group

Description:

Avapritinib 200mg/ day, 28 days a course

Treatment:

Drug: Avapritinib

Daunorubicin/MTZ/Idarubicin+Cytarabine +Venetoclax

Experimental group

Description:

Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2；or Idarubicin 10mg/ m2/d，d1-2；or MTZ 8mg/ m2/d d1-2; Venetoclax 400mg d1-7

Treatment:

Drug: Daunorubicin

Drug: MTZ

Drug: Idarubicin

Drug: Cytarabine

Drug: Venetoclax

Cytarabine+HHT+Venetoclax

Experimental group

Description:

Cytarabine 100mg/ m2/d, d1-5; HHT 2mg/ m2 d1-5; Venetoclax 400mg d1-7

Treatment:

Drug: HHT

Drug: Cytarabine

Drug: Venetoclax

Venetoclax+Azacitidine/Venetoclax+Cytarabine

Experimental group

Description:

Azacitidine75 mg/m2 day1-7；Venetoclax 400mg day1-21 or，Cytarabine 20mg/m2 /day，day1-10； Venetoclax 600mg day1-21

Treatment:

Drug: Cytarabine

Drug: Azacitidine

Drug: Venetoclax