Clinical trial NCT06635681: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: AML (Acute Myelogenous Leukemia)
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-10-10
Enrollment: 1200
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: up to 2 years after the date of the last enrolled participants
Secondary outcomes:
measure: Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry
timeFrame: up to 1 years after the date of the last enrolled participants
measure: CR/CRh/CRi with negative MRD detected by PCR
timeFrame: up to 1 years after the date of the last enrolled participants
measure: overall survival (OS)
timeFrame: up to 2 years after the date of the last enrolled participants
measure: 30-day mortality
timeFrame: within 30 days of the date of the last enrolled participants
measure: 60-day mortality
timeFrame: within 60 days of the date of the last enrolled participants
measure: Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) rate
timeFrame: up to 3 months after the date of the last enrolled participants
measure: Relapse-free survival (RFS)
timeFrame: up to 2 years after the date of the last enrolled participants
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
name: Hui Wei, MD
role: PRINCIPAL_INVESTIGATOR
References: