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

Official title

Efficacy of Venetoclax Combined With Intensive Chemotherapy in Different Subgroups of Acute Myeloid Leukemia : a Multi-center, Single-arm Clinical Trial

Overview

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.

Interventions

• Drug Daunorubicin
  60mg/m2/d d1-3 in Induction therapy
• Drug Cytarabine
  Cytarabine 100mg/m2/d d1-7 in Induction therapy, 2g/m2 q12h d1-3 in Consolidation therapy
• Drug Venetoclax
  100mg d-2, 200mg d-1, 400mg d1-7 in Induction therapy, 400mg d1-7 in Consolidation therapy and Maintenance treatment
• Drug Azacitidine
  75mg/m2/d d1-5

Primary outcome measures

• Event-free survival (EFS) [Time frame: up to 2 years after the date of the last enrolled participants]

Secondary outcome measures (7)

• Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry [Time frame: up to 1 years after the date of the last enrolled participants]
• CR/CRh/CRi with negative MRD detected by PCR [Time frame: up to 1 years after the date of the last enrolled participants]
• overall survival (OS) [Time frame: up to 2 years after the date of the last enrolled participants]
• 30-day mortality [Time frame: within 30 days of the date of the last enrolled participants]
• 60-day mortality [Time frame: within 60 days of the date of the last enrolled participants]
• Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) rate [Time frame: up to 3 months after the date of the last enrolled participants]
• Relapse-free survival (RFS) [Time frame: up to 2 years after the date of the last enrolled participants]

Eligibility criteria

Inclusion criteria

• Patients who meet AML according to WHO (2022) or AML and MDS/AML defined by ICC standards.
• Age ≥14 years old, ≤ 60 years old, male or female.
• The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
• Fulfill the requirements of the following laboratory tests (performed within 7 days prior to treatment) :

• Total bilirubin ≤ 1.5 times the upper limit of normal value (same age);
• AST and ALT≤ 2.5 times the upper limit of normal value (same age);
• Blood creatinine < 2 times the upper limit of normal (same age);
• Myocardial enzymes < 2 times the upper limit of normal (same age);
• 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:

• Acute promyelocytic leukemia with PML-RARA fusion gene
• Acute myeloid leukemia with BCR-ABL fusion gene
• Treated patients (but can receive hydroxyurea or cytarabine to the lower tumor burden).
• Concurrent malignant tumors of other organs (those requiring treatment).
• Active heart disease, defined as one or more of the following:

• A history of uncontrolled or symptomatic angina;
• Myocardial infarction less than 6 months after enrollment;
• Have a history of arrhythmia requiring drug treatment or severe clinical symptoms;
• Uncontrolled or symptomatic congestive heart failure (> NYHA level 2);
• Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).
• Those who were not considered suitable for inclusion by the researchers.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Blood Diseases Hospital — Tianjin

Identifiers

NCT: NCT06635681 · IIT2024074

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗