Comparison of the Efficacy and Safety of Venetoclax in Combination With 3 Days Decitabine (DEC3-VEN) vs. Venetoclax in Combination With Azacitidine (VIALE-A) in the Treatment of Elderly Patients or Unfit, New-diagnosis Acute Myeloid Leukemia Patients

Launched by THE SECOND AFFILIATED HOSPITAL OF KUNMING MEDICAL UNIVERSITY · Oct 3, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness and safety of a new treatment for older patients or those who are not fit for standard chemotherapy and have just been diagnosed with acute myeloid leukemia (AML). Specifically, the trial is comparing two treatment combinations: one that includes Venetoclax and a three-day course of Decitabine, and another that includes Venetoclax with Azacitidine, which is a standard treatment. The goal is to find out if the new combination can help patients live longer without their cancer worsening.

To be eligible for this trial, participants must be at least 60 years old or adults who cannot tolerate standard chemotherapy due to other health issues. They should not have had prior treatment for AML and must meet certain health criteria, which will be evaluated by the study doctors. If you decide to participate, you can expect to be monitored closely during the treatment and follow-up periods. This trial is important because it aims to provide new options for treating AML in patients who may have limited choices.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Subjects suitable for enrollment in this study must meet all of the following criteria.
• • 1. meet the World Health Organization diagnostic criteria (WHO2022 criteria) except APL or carry one of the abnormal karyotypes such as t(8;21)/(RUNX1::RUNX1TI), inv(16)(p13.1q22), t(16;16) (p13.1q22), t(16;16)/CBFβ::myh11), etc. Patients with acute myeloid leukemia other than those with one of the abnormal karyotypes such as t(16;16)/CBFβ::myh11
• • 2. Patients with AML not otherwise classified under the World Health Organization AML classification, except for acute myeloproliferative disorder with myelofibrosis and myeloid sarcoma.
• • 3. Male or female, A: Elderly patients aged \> or = 60 years (unwilling to undergo intense chemotherapy); B: Patients aged \> 18 years who are not candidates for standard-dose chemotherapy, defined as those with at least one of the following comorbidities: 1) Eastern Collaborative Oncology Group Physical Conditioning Grading (ECOG) score of 2 or 3; 2) Chronic heart failure (CHF) requiring treatment or with a left ventricular ejection fraction (LVEF) of ≤ 50%; 3) Chronic heart failure (CHF) requiring treatment or with a left ventricular ejection fraction (LVEF) of ≤ 50%. heart failure (CHF) cardiac history or chronic unstable angina; 3) carbon monoxide diffusing capacity (DLCO) ≤65% or forced expiratory volume in 1 second (FEV1) ≤65%; 4) creatinine clearance of ≥30 mL/min to ≤45 mL/min; and 5) any other condition deemed by the investigator to be incompatible with standard-dose chemotherapy must be reviewed with the study chair prior to study enrollment ;
• • 4. patients have not received prior treatment for AML (except hydroxyurea and Ara-C \<1.0 g/d).
• • 5. Eastern Cooperative Oncology Group Physical Status Assessment (ECOG-PS) score of \<=3.
• 6. pass the requirements for the following laboratory test indices (performed within 7 days prior to treatment):
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• • 1. Aspartate aminotransferase (ALT), alanine aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN), serum bilirubin ≤ 2 x ULN; and serum cardiac enzymes \< 2.0 x ULN; unless considered to be leukemic organ involvement.
• • 2. Creatinine ≥ 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
• • 7.Subjects of childbearing potential must have a negative pregnancy test result within 72 hours prior to the start of treatment, and participating patients must use contraception during trial treatment and for 3 years after completion of treatment.
• • 8. life expectancy greater than 2 months. 9. Informed consent must be signed prior to the start of all specific study procedures, either by the patient himself/herself or by a member of his/her immediate family; in view of the patient's condition, if the patient's own signature would not be conducive to the treatment of his/her condition, the informed consent will be signed by the legal guardian or by a member of the patient's immediate family.
• Exclusion Criteria:
• Subjects may not be enrolled in this study if they meet any of the following criteria:
• • 1. AML with BCR-ABL1; or CML bone marrow acute stage.
• • 2. Treatment-naïve patients (is defined as having received induction chemotherapy in the past, regardless of efficacy).
• • 3. Secondary leukemia (mainly refers to those whose World Health Organization (WHO) AML classification belongs to the subcategory of treatment-related AML and those with a history of prior MDS and/or MPD).
• • 4. concomitant other hematologic diseases (such as hemophilia, myelofibrosis and other investigators considered unsuitable for enrollment; previous blood abnormalities, but ever bone marrow examination except MDS and MPD allowed enrollment).
• • 5、Pregnant or lactating patients. 6, Allergic to any of the drugs involved in this study. 7, Have used strong or moderate CYP7A inducers within 3 days before the start of study treatment.
• • 8, Concomitant malignant tumors of other organs (those requiring treatment). 9, Significantly abnormal hepatic or renal function beyond the enrollment criteria.
• 10, Active heart disease, defined as one or more of the following:
• • 1. Myocardial infarction less than 6 months from study entry;
• • 2. A history of arrhythmia requiring drug therapy or severe clinical symptoms;
• • 3. Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2); 10, patients with severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis), known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
• • 11. Subjects with evidence of central nervous system leukemia prior to treatment.
• • Subjects with epilepsy, dementia, or other abnormal mental states that require medication and who are unable to understand or follow the regimen.
• • 13, Conditions that limit oral drug intake or gastrointestinal absorption. 14, Subjects who, in the opinion of the investigator, are not suitable for enrollment