Clinical trial NCT05471700: Single Arm Study of Azacitidine and Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients
Official title: To Evaluate Safety and Efficacy of Azacitidine Combination With Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients：A Multicenter, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leukemia, Myeloid, Acute
Keywords: Acute Myeloid Leukemia
Newly Diagnosed AML
Azacitidine
Venetoclax
Induction Therapy
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
First posted: 2022-07-25
Enrollment: 40
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to evaluate the safety and efficacy of Azacytidine in combination with Venetoclax in patients with newly diagnosed fit acute myeloid leukemia.

Detailed description: The Study Drug:

Azacitidine is a DNA Demethylated drug, which is approvd for treatment of elderly AML patients Venetoclax targets the anti-apoptotic protein Bcl-2 and the process of oxidative phosphorylation to induce apoptosis of leukemia cells and exhibits anti-tumor activity.

Study Group:

single arm: AZA plus Venetoclax

Study Drug Administration:

Each course is 28 days long. Venetoclax is taken once daily by oral. The doses of Venetoclax is 100 mg on Day 1, 200 mg on Day 2, reaching a target dose of 400 mg on Day 3 and continuing through Day 28. If concomitantly receiving azoles, the dose of Venetoclax will be adjusted according to the instructions. Azacitidine is taken 75mg/m2 on Days 1-7. Subjects would received 1-2 cycles induction therapy. Once get remission, subjects would received the same indution therapy of middle to high dose of cytarabine based chemotherapy at the discretion of the physician for consolidation. Allo-HSCT is suggested for subjects with the moderate to adverse ELN2017 risk.

Study Visit:

After treatment, relapse and survival will be followed monthly by telephone, on-site visits, and/or study medical records for up to two years (calculated from the first day of induction therapy); Thereafter follow-up every 3 months for one year.

Eligibility criteria: Inclusion Criteria:

* 1.Age 45 to 65 years old,both male and female
* 2.Be able to understand and sign informed consent
* 3.Untreated AML patients (non-APL) diagnosed according to the 2016 World Health Organization (WHO) classification and diagnostic criteria for acute myeloid leukemia
* 4.Patients with an ECOG performance status 0,1,2 or 3
* 5.Expected survival time≥3 months
* 6.Laboratory indicators meet the following standards:

  1. Bilrubin, ALT and AST were all less than 3 times the upper limit of normal within 7 days before the first day of treatment
  2. Serum creatinine clearance rate is greater than 30ml/min

Exclusion Criteria:

* 1.patients participating in other interventional or observational clinical studies currently
* 2.Patients has a history of myeloproliferative neoplasm \[MPN\]
* 3.Patients with acute promyelocytic leukemia
* 4.Active CNS involvement in patients with acute myeloid leukemia
* 5.Patients with active hepatitis B or C, HIV infection before enrollment
* 6.Cardiovascular status of patients evaluate by NYHA classification method \> 2
* 7.Patients have chronic respiratory disease requiring continuous oxygen treatment, or any sitiuation investigator believes will adversely affect this study (including renal, neurological, psychiatric, endocrine, metabolic, immune, hepatic, cardiovascular disease and known history of allergy to any study drug)
* 8.Patients suffering from malabsorption syndrome or other diseases that prevent the enteral route of administration
* 9.patients present with an uncontrolled systemic infection (viral, bacterial, or fungal)
* 10.Patients with a history of other malignancies within 2 years before enrollment, except for the following cases:

  1. Adequately treated carcinoma in situ of the cervix or carcinoma of the breast
  2. Basal cell carcinoma or localized squamous cell carcinoma of skin

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 36 months
Secondary outcomes:
measure: Minimal residual disease (MRD) negative response rate
timeFrame: Up to 36 months
measure: Duration of Remission (DOR)
timeFrame: Up to 36 months
measure: Allogeneic Hematopoietic Stem Cell Transplantation Rate
timeFrame: Up to 36 months
measure: Overall Survival (OS)
timeFrame: Up to 36 months
measure: Event-Free Survival (EFS)
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guandong
Study officials:
affiliation: Zhujiang Hospital
name: Yuhua Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: