Efficacy of Venetoclax Combined with Intensive Chemotherapy in Different Subgroups of AML

NCT ID: NCT06635681

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 1200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-29
• Study Completion Date: 2028-10-01

Brief Summary

Acute myeloid leukemia (AML) is a common hematological malignancy. Intensive chemotherapy is the main treatment in fit patients.

Retrospective studies have shown that Venetoclax is highly effective in elder AML patients with IDH2 and NPM1 mutations while in those with TP53 and FLT3 mutations, the combination of azacitidine with Venetoclax showed an increased remission rate without improved survival.

Since AML is a highly heterogeneous disease, it is not clear which genetic type of adult AML patients would benefit from Venetoclax combined with intensive chemotherapy.

Therefore, this study intends to conduct a phase II clinical trial to investigate the efficacy of intensive chemotherapy combined with Venetoclax in adult AML patients, and reveal the efficacy of Venetoclax added to chemotherapy regimens for AML with different cytogenetic and molecular subgroups.

Detailed Description

Patients will receive 1 course of intensive chemotherapy combined with venetoclax for induction and those who achieved complete remission will receive 3 courses of intermediate-dose cytarabine combined with Venetoclax for consolidation. After consolidation therapy, Venetoclax in combination with azacitidine will be applied for 6 courses as maintenance treatment. Allogeneic hematopoietic stem cell transplantation is recommended for high-risk groups and intermediate-risk with positive measurable residual disease.

Conditions

AML (Acute Myelogenous Leukemia)

Study Design

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

Study Groups

venetoclax combined with intensive chemotherapy

Induction therapy: daunorubicin, cytarabine, combined with venetoclax for 1 course.

Consolidation therapy: cytarabine combined with venetoclax for 3 courses.

Maintenance therapy: azacitidine combined with venetoclax for 6 courses.

Group Type: EXPERIMENTAL

combined chemotherapy

Intervention Type: DRUG

Induction therapy(1 cycle):

Daunorubicin 60mg/m2/d d1-3 Cytarabine 100mg/m2/d d1-7 Venetoclax 100mg d-2, 200mg d-1, 400mg d1-7 If the first course of treatment did not result in CR, patients with therapeutic target could be treated with targeted drugs, and the patients without targets would be treated with HAV regimen: Cytarabine 100mg/m2/d, d1-5, Homoharringtonine 2mg/m2 d1-5, Venetoclax 100mg d-2, 200mg d-1, 400mg d1-7.

Consolidation therapy(3 cycles):

Cytarabine 2g/m2 q12h d1-3 Venetoclax 400mg d1-7 For patients with CBF and CEBPA dual mutations, the dose of cytarabine is 3g/m2.

Maintenance treatment(6 cycles):

Azacitidine 75mg/m2/d d1-5 Venetoclax 400mg d1-7

Allogeneic hematopoietic stem cell transplantation is recommended for high-risk groups and intermediate-risk with positive measurable residual disease.

Interventions

combined chemotherapy

Induction therapy(1 cycle):

Daunorubicin 60mg/m2/d d1-3 Cytarabine 100mg/m2/d d1-7 Venetoclax 100mg d-2, 200mg d-1, 400mg d1-7 If the first course of treatment did not result in CR, patients with therapeutic target could be treated with targeted drugs, and the patients without targets would be treated with HAV regimen: Cytarabine 100mg/m2/d, d1-5, Homoharringtonine 2mg/m2 d1-5, Venetoclax 100mg d-2, 200mg d-1, 400mg d1-7.

Consolidation therapy(3 cycles):

Cytarabine 2g/m2 q12h d1-3 Venetoclax 400mg d1-7 For patients with CBF and CEBPA dual mutations, the dose of cytarabine is 3g/m2.

Maintenance treatment(6 cycles):

Azacitidine 75mg/m2/d d1-5 Venetoclax 400mg d1-7

Allogeneic hematopoietic stem cell transplantation is recommended for high-risk groups and intermediate-risk with positive measurable residual disease.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients who meet AML according to WHO (2022) or AML and MDS/AML defined by ICC standards.

2. Age ≥14 years old, ≤ 60 years old, male or female.

3. The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.

4. Fulfill the requirements of the following laboratory tests (performed within 7 days prior to treatment) :

1. Total bilirubin ≤ 1.5 times the upper limit of normal value (same age);

2. AST and ALT≤ 2.5 times the upper limit of normal value (same age);

3. Blood creatinine < 2 times the upper limit of normal (same age);

4. Myocardial enzymes < 2 times the upper limit of normal (same age);

5. Left ventricular ejection fraction &gt;50% by measure of echocardiogram (ECHO). Informed consent must be signed before the commencement of all specific study procedures, and signed by the patient himself or his immediate family. Considering the patient&#39;s condition, if the patient&#39;s signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient&#39;s immediate family.

Exclusion Criteria

Subjects who meet any of the following criteria are excluded from the study:

1. Acute promyelocytic leukemia with PML-RARA fusion gene

2. Acute myeloid leukemia with BCR-ABL fusion gene

3. Treated patients (but can receive hydroxyurea or cytarabine to the lower tumor burden).

4. Concurrent malignant tumors of other organs (those requiring treatment).

5. Active heart disease, defined as one or more of the following:

1. A history of uncontrolled or symptomatic angina;

2. Myocardial infarction less than 6 months after enrollment;

3. Have a history of arrhythmia requiring drug treatment or severe clinical symptoms;

4. Uncontrolled or symptomatic congestive heart failure (> NYHA level 2);

6. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).

7. Those who were not considered suitable for inclusion by the researchers.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hui Wei, MD

Role: PRINCIPAL_INVESTIGATOR

Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Locations

Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hui Wei, MD

Role: CONTACT

weihui@ihcams.ac.cn

13132507161

Facility Contacts

hui wei, MD

Role: primary

weihui@ihcams.ac.cn

86-13132507161

Other Identifiers

IIT2024074

Identifier Type: -

Identifier Source: org_study_id