Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML

NCT ID: NCT06429098

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2027-12-31

Brief Summary

This investigator-initiated, single-arm, phase II trial is aimed to evaluate the efficacy and safety of a venetoclax-based, anthracycline-free regimen in patients with newly diagnosed CBFβ::MYH11-positive acute myeloid leukemia.

Detailed Description

Primary Objectives:

To determine the CR (complete remission) / CRi (complete remission with incomplete blood count recovery) rate of 2 cycles of VEN/HMA in patients with newly diagnosed (ND) CBFβ::MYH11-positive acute myeloid leukemia(AML).

Secondary Objectives:

1. To determine the overall response rate (ORR) of 2 cycles of VEN/HMA in patients with ND CBFβ::MYH11-positive AML.

2. To determine the safety of the combination regimen.

3. To study the trajectories of molecular measurable residual disease (MRD) during the therapy.

4. To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen.

5. To assess the duration of response, overall survival (OS) and event free survival (EFS) of patients.

OUTLINE:

INDUCTION:

Patients with newly diagnosed CBFβ::MYH11(+) AML receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5.

CONSOLIDATION:

Patient fitness will be reassessed according to the Ferrara criteria if CR or CRi is achieved after 2 cycles of VEN/HMA. Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Venetoclax, Azacitidine/Decitabine/, Cytarabine

INDUCTION: Patients receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5.

CONSOLIDATION: Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Given PO, once daily. Treatment in cycle 1, the dose is 100 mg on day 1, then ramp up to 400mg. In all subsequent cycles, the dose of venetoclax is initiated at 400 mg daily.

azacitidine

Intervention Type: DRUG

Given SC

decitabine

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Interventions

Venetoclax

Given PO, once daily. Treatment in cycle 1, the dose is 100 mg on day 1, then ramp up to 400mg. In all subsequent cycles, the dose of venetoclax is initiated at 400 mg daily.

Intervention Type: DRUG

azacitidine

Given SC

Intervention Type: DRUG

decitabine

Given IV

Intervention Type: DRUG

Cytarabine

Given IV

Intervention Type: DRUG

Other Intervention Names

ABT-199; ABT199; Venclexta; 5 AZC; 5-AZC; Dacogen; 1-.beta.-Cytosine arabinoside; Ara-C

Eligibility Criteria

Inclusion Criteria

1. Adults ≥ 18 years.

2. Newly diagnosed CBFβ::MYH11(+) AML.

3. Performance status 0-3 on the Eastern Cooperative Oncology Group (ECOG) Scale.

4. Subject must voluntarily sign and date an informed consent, prior to the initiation of any screening or study-specific procedures.

Ferrara's criteria are used to determine whether a patient is unfit, and a patient is deemed unfit if at least one of the following criteria is met:

1. Age>75 years.

2. There are serious underlying heart, lung, kidney, liver complications.

3. There are active infections that do not respond to anti-infective therapy.

4. There is cognitive impairment.

5. Other comorbidities that the doctor determines are not suitable for intensive chemotherapy.

Exclusion Criteria

1. Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental or targeted drug therapy for AML (except oral hydroxyurea and/or leukocytometry to reduce white blood cell count).

2. Pregnant or lactating women.

3. To the knowledge of the subject and investigator, subject may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or be unable to comply with the required study procedures.

4. Other conditions deemed unsuitable for participation in this study by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ying Wang

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Soochow University

Locations

Ethical Committee of the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ying Wang

Role: CONTACT

wangying77@suda.edu.cn

008613656214782

Facility Contacts

Zhou-lin Lu

Role: primary

008613914086271

Ying Wang

Role: primary

wangying77@suda.edu.cn

008613656214782

Other Identifiers

2023371

Identifier Type: -

Identifier Source: org_study_id