AZA + Venetoclax as Maintenance Therapy in Younger Adults With AML in First Remission

Randomized, Multicenter, Phase 3 Study of Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With AML in Remissionin Younger Adults With Favorable-risk AML in First Remission After Conventional Chemotherapy

This phase III trial is conducted to evaluate if azacitidine in combination with venetoclax as maintenance therapy improves relapse-free survival (RFS) for younger adults with favorable-risk acute myeloid leukemia (AML) who remained in first complete remission (CR1) following intensive consolidation.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML) in Remission
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine; Other: Supportive care

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Suning Chen; Phone Number: +86-13814881746; Email: chensuning@sina.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • First Affiliated Hospital of Soochow University
      • Contact: Suning Chen, PhD; Phone Number: +8613814881746; Email: chensuning@sina.com
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
      • Contact: Suning Chen, Professor; Phone Number: 13814881746; Email: chensuning@sina.com
      • Principal Investigator: Suning Chen, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of favorable-risk acute myeloid leukemia (AML) according to revised 2017 European LeukemiaNet genetic risk stratification and are not immediate candidates for allogeneic stem cell transplant.
2. Aged 18-64 years.
3. Patients who have received remission induction therapy and 3-4 HiDAC or medium-dose cytarabine-based consolidation and are in their first remission.
4. ECOG performance status of < or = 3.

5. Adequate organ function as follows:

   1. Serum total bilirubin < or = to 3 X the Upper Limit of Normal (ULN)
   2. Aspartate Transaminase and alanine transaminase < or = to 3 x ULN
   3. Ccr（Creatinine Clearance Rate) > or ＝60 ml/min
   4. Left ventricular ejection fraction > or ＝50% determined by ultrasound.
6. For females of childbearing age, they should have a negative serum or urine pregnancy test within 10 to 14 days of enrolling.
7. For males of childbearing age, they should take effective contraceptive methods throughout the treatment period and up to 30 days after discontinuing treatment.
8. Ability to understand and sign informed consent.

Exclusion Criteria:

1. Acute promyeloid leukemia.
2. Patients with active central nervous system (CNS) leukemia.
3. Previously diagnosed with myelodysplastic syndrome (MDS) or myeloproliferative neoplasm(MPN) and progressed to AML.
4. Patients with other progressive malignancies.
5. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled and/or active systemic infection (viral, bacterial or fungal).
6. Patients who have participated in other trials within 30 days before signing the informed consent.
7. Females who are pregnant or lactating or intending to become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (azacytidine+venetoclax); Participants will receive azacytidine QD, on Days 1-5 and venetoclax QD, on Days 1-14 of each 28-day cycle for 8 cycles.	Drug: Venetoclax; Given PO; Other Names: Venclexta; ABT-199; GDC-0199; Drug: Azacitidine; Given SC; Other Names: 5-Azacytidine; Other: Supportive care; Patients will receive disease monitoring and supportive care for any complication.
Experimental: Comparator ( best supportive care); Participants will receive observation and supportive care during remission.	Other: Supportive care; Patients will receive disease monitoring and supportive care for any complication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)	RFS is defined as the number of days from CR/CRi to the date of relapse or the date of death from any cause, whichever comes first.	From date of complete remission (CR) or complete remission with incomplete count recovery (CRi), to relapse or death from any cause, up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve Minimal Minimal Residual Disease (MRD) Negative Conversion	The MRD conversion rate is defined as the percentage of participants deemed MRD positive (≥ 10^-3) at study initiation who converted to MRD of < 10^-3 in the bone marrow after randomization or initiation of treatment.	Measured From Baseline to approximately 3 years
Complete remission duration (CRd)	CRd is defined as time from CR/CRi until date of confirmed relapse	From date of CR/CRi to approximately 3 years
Overall Survival (OS)	OS is defined as the number of days from the date of study treatment to the date of death.	Time from treatment to death from any cause, up to approximately 3 years
Event free survival (EFS)	EFS is defined as time from the start of study treatment until date of first confirmed relapse, withdrawal from study due to adverse event, or death due to any cause,	Time from treatment to relapse，withdrawal from study due to adverse event and death from any cause, up to approximately 3 years
Incidence of adverse events	The NCI Common Toxicity Criteria (CTCAE 5.0) is used to grade adverse events.	Time from treatment to approximately 3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Suning Chen, First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2022
• Primary Completion (Anticipated): June 1, 2028
• Study Completion (Anticipated): June 1, 2030

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• 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: SZ-AML124

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