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

NCT06073730 | Unknown Phase 3

• 1 other identifier: SHEN-PJ-KE-2023-223
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

Combining the results of previous studies and based on the clinical practice in our center, we designed the Venetoclax in combination with 3days-Decitabine regimen for induction therapy in elderly or unfit AML patients with a primary diagnosis, and set Venetoclax in combination with Azacitidine (VIALE-A) as a control group to compare the efficacy and safety and to provide evidence for the optimal selection of the clinical treatment regimen. PRIMARY ENDPOINT: To assess whether Venetoclax in combination with 3 days-diascitabine versus standard dose Venetoclax in combination with azacitidine improves event-free survival (EFS) in elderly or adult patients with unfit AML during the maximum follow-up period. Event-free survival was defined as the absence of events such as treatment failure, intolerance withdrawal, all-cause death, or achievement of CR or CRi, or relapse after MLFS, whichever occurred first, between patients' randomization and the maximum follow-up period. Treatment failure was defined as failure to achieve CR or CRi, MLFS after 2 courses of induction therapy.

Conditions

Elderly AML Patients; Unfit, New-diagnosis AML; Acute Myeloid Leukemia; Venetoclax; Decitabine

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  Event-free survival was defined as the absence of events such as treatment failure, intolerance withdrawal, all-cause death, or relapse after achieving CR or CRi, MLFS, whichever occurred first, between patients' randomization and the maximum follow-up period. Treatment failure was defined as failure to achieve CR or CRi, MLFS after 2 courses of induction therapy.

  up to 12 months

Secondary Outcomes (3)

• overall survival rate

  up to 12 months

• CR/CRi rate

  up to 12 months

• First course CR/CRi rate

  up to 1 months

Study Arms (2)

Venetoclax in combination with Decitabine (+-sorafenib)

EXPERIMENTAL

Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-14 Decitabine (DEC) 20mg/m2/q8h, d4-6 (infusion time \>2h) Sorafenib 600mg/d, d8-14 (FLT3/ITD mutation positive patients)

Procedure: Experimental: Venetoclax in combination with Decitabine (+-sorafenib)

Standard dose of Venetoclax + Azacitidine

ACTIVE COMPARATOR

Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-28 Azacitidine (AZA) 75mg/m2/d, d3-9

Procedure: Active Comparator: Standard dose of Venetoclax + Azacitidine

Interventions

Experimental: Venetoclax in combination with Decitabine (+-sorafenib) PROCEDURE

Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-14 Decitabine (DEC) 20mg/m2/q8h, d4-6 (infusion time \>2h) Sorafenib 600mg/d, d8-14 (FLT3/ITD mutation positive patients)

Also known as: DEC3-VEN

Venetoclax in combination with Decitabine (+-sorafenib)

Active Comparator: Standard dose of Venetoclax + Azacitidine PROCEDURE

Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-28 Azacitidine (AZA) 75mg/m2/d, d3-9

Standard dose of Venetoclax + Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects suitable for enrollment in this study must meet all of the following criteria.
• 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
• Patients with AML not otherwise classified under the World Health Organization AML classification, except for acute myeloproliferative disorder with myelofibrosis and myeloid sarcoma.
• 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 ;
• patients have not received prior treatment for AML (except hydroxyurea and Ara-C \<1.0 g/d).
• Eastern Cooperative Oncology Group Physical Status Assessment (ECOG-PS) score of \<=3.
• pass the requirements for the following laboratory test indices (performed within 7 days prior to treatment):
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• 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.
• Creatinine ≥ 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
• 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.
• \. 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.

You may not qualify if:

• Subjects may not be enrolled in this study if they meet any of the following criteria:
• AML with BCR-ABL1; or CML bone marrow acute stage.
• Treatment-naïve patients (is defined as having received induction chemotherapy in the past, regardless of efficacy).
• 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).
• 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).
• 、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.
• , Concomitant malignant tumors of other organs (those requiring treatment). 9, Significantly abnormal hepatic or renal function beyond the enrollment criteria.
• , Active heart disease, defined as one or more of the following:
• Myocardial infarction less than 6 months from study entry;
• A history of arrhythmia requiring drug therapy or severe clinical symptoms;
• 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.
• \. 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.
• , Conditions that limit oral drug intake or gastrointestinal absorption. 14, Subjects who, in the opinion of the investigator, are not suitable for enrollment

Sponsors & Collaborators

• The Second Affiliated Hospital of Kunming Medical University: lead

Study Sites (1)

The Second Affiliated Hospital of Kunming Medical University.

Kunming, Yunnan, China

Location

Related Publications (12)

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; Sorafenib; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 10, 2023
• Study Start: November 1, 2023
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)