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

NCT06635681 | Recruiting Phase 2

• 1 other identifier: IIT2024074
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

AML (Acute Myelogenous Leukemia)

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  All patients definitions for the trial; From the date of enrollment to the time of treatment failure after two courses of induction therapy, recurrence after CRc, date of all-cause death, or the date of last survival follow-up.

  up to 2 years after the date of the last enrolled participants

Secondary Outcomes (7)

• Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry

  up to 1 years after the date of the last enrolled participants

• CR/CRh/CRi with negative MRD detected by PCR

  up to 1 years after the date of the last enrolled participants

• overall survival (OS)

  up to 2 years after the date of the last enrolled participants

• 30-day mortality

  within 30 days of the date of the last enrolled participants

• 60-day mortality

  within 60 days of the date of the last enrolled participants

Study Arms (1)

venetoclax combined with intensive chemotherapy

EXPERIMENTAL

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.

Drug: combined chemotherapy

Interventions

combined chemotherapy 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.

venetoclax combined with intensive chemotherapy

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Antineoplastic Combined Chemotherapy Protocols

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antineoplastic Protocols; Clinical Protocols; Therapeutics; Drug Therapy; Drug Therapy, Combination

Study Officials

• Hui Wei, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 10, 2024
• Study Start: September 29, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

CN (1)