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

Phase 2

Recruiting

• Conditions: Acute Myeloid Leukemia (AML) in Remission
• Interventions: Drug: Azacitidine; Drug: Venetoclax; Other: Supportive care

• Registration Number: NCT05404906
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-05-31
• Study First Posted: 2022-06-03
• Study Start: 2022-06-25
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-18
• Last Update Posted: 2022-08-19
• Primary Completion: 2028-06
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 124

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment (azacytidine+venetoclax)	Azacitidine	Participants will receive azacytidine QD, on Days 1-5 and venetoclax QD, on Days 1-14 of each 28-day cycle for 8 cycles.
Treatment (azacytidine+venetoclax)	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.
Treatment (azacytidine+venetoclax)	Supportive care	Participants will receive azacytidine QD, on Days 1-5 and venetoclax QD, on Days 1-14 of each 28-day cycle for 8 cycles.
Comparator ( best supportive care)	Supportive care	Participants will receive observation and supportive care during remission.

Primary Outcome Measures

Name	Time	Method
Relapse-free survival (RFS)	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	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Time from treatment to approximately 3 years	The NCI Common Toxicity Criteria (CTCAE 5.0) is used to grade adverse events.
Complete remission duration (CRd)	From date of CR/CRi to approximately 3 years	CRd is defined as time from CR/CRi until date of confirmed relapse
Overall Survival (OS)	Time from treatment to death from any cause, up to approximately 3 years	OS is defined as the number of days from the date of study treatment to the date of death.
Event free survival (EFS)	Time from treatment to relapse，withdrawal from study due to adverse event and death from any cause, up to approximately 3 years	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,
Percentage of Participants Who Achieve Minimal Minimal Residual Disease (MRD) Negative Conversion	Measured From Baseline to approximately 3 years	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.

Trial Locations

Locations (2)

First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology; 🇨🇳 Suzhou, Jiangsu, China