Single Arm Study of Azacitidine and Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05471700
• Other study ID #: AZA+Venetoclax
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: July 2023
• Source: Zhujiang Hospital
• Contact: Huang Rui, Doctor
• Phone: +8615918528317
• Email: Rachelchn[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Azacitidine
Subjects will receive Azacitidine 75 mg/m2 on days 1-7.Each course is 28 days long.
• Venetoclax
Subjects would receive Venetoclax 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. Each course is 28 days long.

Locations

Country	Name	City	State
China	Nanfang Hospital of Southern Medical University	Guanzhou	Guandong

Sponsors (1)

Lead Sponsor	Collaborator
Zhujiang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve the CR + CRi + Partial Remission (PR) as evaluated by the investigator.	Up to 36 months
Secondary	Minimal residual disease (MRD) negative response rate	The number of subjects who obtained MRD negative as a percentage of all evaluable subjects.	Up to 36 months
Secondary	Duration of Remission (DOR)	From the first achievement of PR, CR, or CRi to time of disease progression	Up to 36 months
Secondary	Allogeneic Hematopoietic Stem Cell Transplantation Rate	Proportion of subsequent allogeneic hematopoietic stem cell transplantation in intermediate-risk and adverse-risk patients	Up to 36 months
Secondary	Overall Survival (OS)	From start of protocol treatment to time of death due to any cause, or until last follow-up	Up to 36 months
Secondary	Event-Free Survival (EFS)	From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier; or until last follow-up	Up to 36 months