Azacitidine Combined With Venetoclax and ATRA in Newly Diagnosed AML

A Single Arm Study to Evaluate the Safety and Efficiency of Azacitidine (AZA) Combination With Venetoclax and ATRA in Patients With Newly Diagnosed Acute Myeloid Leukemia

This is a single arm study to evaluate the safety and efficiency of azacitidine (AZA) combination with venetoclax and ATRA in Patients With Newly diagnosed acute myeloid leukemia. Azacitidine, venetoclax and ATRA, may stop the growth of cancer cells, either by demethylation, by promoting cells differentiation or by killing the cells.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Azacitidine Combined With Venetoclax and ATRA group

Detailed Description

This study include newly diagnosed AML patients who will accept the therapy with AZA combined with venetoclax and ATRA: (1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28, every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month till progression;

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yue Han, PhD; Phone Number: 8613901551669; Email: hanyue@suda.edu.cn
• Study Contact Backup: Name: Chengyuan Gu, MD; Phone Number: 8618068016508; Email: guchengyuan@suda.edu.cn

Study Locations

• China
  • Suzhou, China
    • Recruiting
    • The First Affiliated Hospital of Soochow University
    • Contact: Chengyuan Gu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed AML according to the WHO (2016) classification of acute myeloid leukemia.
• Age ≥ 18years.
• ECOG score: 0-3.
• White blood cell count ≤ 25*10^9/L
• Total bilirubin ≤ 3X the institutional upper limit of normal if attributable to hepatic infiltration by neoplastic disease
• AST (SGOT) and ALT (SGPT) ≤ 3X the institutional upper limit of normal
• Creatinine clearance ≥30ml/min

Exclusion Criteria:

• Pregnancy or lactation.
• Acute promylocytic leukemia or chronic myeloid leukemia in blast crisis.
• Another malignant disease.
• Uncontrolled active infection.
• Left ventricular ejection fraction < 0.3 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
• Active hepatitis B or hepatitis C infection.
• HIV infection.
• Other commodities that the investigators considered not suitable for the enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AVA（Azacitidine Combined With Venetoclax and ATRA）group; (1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28,every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month untill progression;

Drug: Azacitidine Combined With Venetoclax and ATRA group; AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28,every 28 days for up to 2 cycles as the inductive therapy.ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles for consolidate therapy.ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month for Maintenance therapy; Other Names: AVA group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of the bone marrow complete response	Rate of the bone marrow complete response after 1 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 1 cycle of inductive therapy	after completion of one induction courses (1st Induction Course is 28 days) and before starting of the 2nd cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of the bone marrow complete response after 2 cycle of inductive therapy	Rate of the bone marrow complete response after 2 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 2 cycle of inductive therapy	after completion of two induction courses (1st Induction Course is 28 days) and before starting of the 1st Consolidation cycle
Minimal Residual Disease (MRD) response	MRD response in bone marrow at the end of 2nd cycle	after completion of two induction courses (one Course is 28 days) and before starting of the 1st Consolidation cycle
Overall Survival (OS)	time from randomization to death from any cause	2 years
Event Free Survival（EFS）	time from randomization to the relapse ,death or drug is unacceptably toxic	2 years
Number of adverse events	adverse events are evaluated with CTCAE V5.0.	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Yue Han, PhD, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: November 25, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: AML; Venetoclax; Azacitidine; ATRA
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: SOOCHOW-HY-2022-11-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No