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

Trial Title: Efficacy of Venetoclax Combined with Intensive Chemotherapy in Different Subgroups of AML

NCT ID: NCT06635681

Condition: AML (Acute Myelogenous Leukemia)

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: combined chemotherapy
Description: 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.
Arm group label: venetoclax combined with intensive chemotherapy

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.

Criteria for 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 >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'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: 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.

Gender: All

Minimum age: 14 Years

Maximum age: 60 Years

Healthy volunteers: No

Locations:

Facility:
Name: Blood Diseases Hospital

Address:
City: Tianjin
Zip: 300020
Country: China

Status: Recruiting

Contact:
Last name: hui wei, MD

Phone: 86-13132507161
Email: weihui@ihcams.ac.cn

Start date: September 29, 2024

Completion date: October 1, 2028

Lead sponsor:
Agency: Institute of Hematology & Blood Diseases Hospital, China
Agency class: Other

Source: Institute of Hematology & Blood Diseases Hospital, China

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06635681