Daunorubicin + Cytarabine + Venetoclax in de Novo AML

Official title

Daunorubicin Plus Cytarabine 3+5 Regimen Combined With Venetoclax in de Novo Patients With Acute Myeloid Leukemia: a Single Center, Open-label, Controlled Study

Overview

This study is a non-profit, prospective, single-center, open-label, controlled clinical trial aimed at evaluating the efficacy of the daunorubicin, cytarabine, and venetoclax (DAV) regimen in previously untreated adult AML patients eligible for intensive chemotherapy.The combination of daunorubicin administered for 3 consecutive days and cytarabine for 7 consecutive days constitutes the classic "3+7" induction chemotherapy regimen for AML patients eligible for chemotherapy. The addition of venetoclax to the "3+7" regimen has shown promising efficacy in newly diagnosed AML patients suitable for intensive therapy. However, this approach is associated with increased adverse reactions. Based on current clinical studies, we propose a modified approach involving reduced-dose chemotherapy combined with venetoclax for AML treatment, aiming to achieve optimal efficacy while effectively reducing adverse reactions.

Detailed description

PRIMARY OBJECTIVE:

1\. To evaluate the efficacy of the regimen, as defined by complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), morphological leukemia-free state (MLFS), and partial remission (PR).

SECONDARY OBJECTIVES:

1. To evaluate the long-term effectiveness and durability of the treatment of the regimen, as defined by 1-year overall survival (OS), 1-year event-free survival (EFS), and duration of remission (DOR). 2. To evaluate the safety of the regimen, as defined by Grade 3-4 clinical adverse events (AEs), incidence of laboratory abnormalities, and treatment-related mortality (TRM).

OUTLINE:

* The regimen for the control group includes:(Daunorubicin, Cytarabine)

* Daunorubicin: 60 mg/(m²·d) on days 1 to 3 * Cytarabine: 100 mg/(m²·d) on days 1 to 7 * The experimental group's "DAV" regimen includes: (Daunorubicin, Cytarabine, Venetoclax)

* Daunorubicin: 40 mg/(m²·d) on days 1 to 3 * Cytarabine: 100 mg/(m²·d) on days 1 to 5 * Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14 * The "DAV" regimen is designed to shorten the duration of induction chemotherapy while extending the application period of venetoclax, aiming to improve efficacy while reducing adverse effects.

Interventions

• Drug (Daunorubicin, Cytarabine, Venetoclax)
  * Drugs：Daunorubicin * Dosage: 40 mg/(m²·d) on days 1 to 3 * Other names: Cerubidine, Daunomycin, Rubidomycin * Drugs：Cytarabine * Dosage: 100 mg/(m²·d) on days 1 to 5 * Other names: Ara-C, Cytosine Arabinoside, Cytosar-U * Drugs：Venetoclax * Dosage: 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14 * Other names: ABT-199, Venclexta, Venclyxto
• Drug (Daunorubicin, Cytarabine)
  * Drugs：Daunorubicin * Dosage: 60 mg/(m²·d) on days 1 to 3 * Other names: Cerubidine, Daunomycin, Rubidomycin * Drugs：Cytarabine * Dosage: 100 mg/(m²·d) on days 1 to 7 * Other names: Ara-C, Cytosine Arabinoside, Cytosar-U

Primary outcome measures

• Overall response rate [Time frame: End of cycle 2 (each cycle is 14 days)]

Secondary outcome measures (4)

• Overall survival (OS) [Time frame: 1-Year Follow-up]
• Event-free survival (EFS) [Time frame: 1-Year Follow-up]
• duration of remission (DOR) [Time frame: 1-Year Follow-up]
• Incidence of adverse events [Time frame: 1-Year Follow-up]

Eligibility criteria

Inclusion Criteria:(All of the following criteria must be met.)

Patients with newly diagnosed AML based on FAB classification and flow cytometry standards who are eligible for intensive chemotherapy:

• Age between 18 and 59 years;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or 3;
• Expected survival time of ≥3 months;
• None of the following severe cardiac, pulmonary, hepatic, or renal conditions:

• History of heart disease requiring treatment for congestive heart failure, or an ejection fraction ≤50%, or chronic stable angina;
• Pulmonary diffusing capacity of carbon monoxide (DLCO) ≤65%, or forced expiratory volume in 1 second (FEV1) ≤65%;
• Moderate liver impairment with total bilirubin >1.5 to ≤3.0 × the upper limit of normal (ULN);
• Creatinine clearance ≥30 mL/min to <45 mL/min;
• Has not received radiotherapy, chemotherapy, targeted therapy, or hematopoietic stem cell transplantation within 4 weeks prior to enrollment;
• Has other comorbidities that, in the physician's judgment, make intensive chemotherapy unsuitable;
• Is capable of understanding and willing to sign the informed consent form for this study.

Exclusion Criteria:(Any of the following criteria will exclude the patient from participation)

• Presence of other malignancies;
• Prior treatment with venetoclax or azacitidine;
• History of angioplasty or stent placement within 12 months prior to signing the informed consent, or a history of myocardial infarction, unstable angina, or other clinically significant heart disease;
• Clinically uncontrolled active infection (including bacterial, fungal, or viral infections);
• Pregnant or breastfeeding women;
• Participation in any other clinical trial within 3 months prior to signing the informed consent;
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Hematology, The First Affiliated Hospital of Anhui Medical University, 218 J — Hefei

Identifiers

NCT: NCT06697327 · PJ 2023-09-19

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗