Azacitidine Combined With Venetoclax and ATRA in Newly Diagnosed AML

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05654194

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Azacitidine Combined With Venetoclax and ATRA group	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Rate of the bone marrow complete response [after completion of one induction courses (1st Induction Course is 28 days) and before starting of the 2nd cycle]
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

Secondary Outcome Measures

Rate of the bone marrow complete response 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]
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
Minimal Residual Disease (MRD) response [after completion of two induction courses (one Course is 28 days) and before starting of the 1st Consolidation cycle]
MRD response in bone marrow at the end of 2nd cycle
Overall Survival (OS) [2 years]
time from randomization to death from any cause
Event Free Survival（EFS） [2 years]
time from randomization to the relapse ,death or drug is unacceptably toxic
Number of adverse events [2 years]
adverse events are evaluated with CTCAE V5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.