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

Study of A Venetoclax-based, Anthracycline-free Regimen in Patients With Newly Diagnosed CBFβ::MYH11-positive Acute Myeloid Leukemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: decitabine; Drug: azacitidine; Drug: Venetoclax

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
    • Suzhou, Jiangsu, China, 215000
      • Ethical Committee of the First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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: 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.

Drug: Cytarabine; Given IV; Other Names: Ara-C; 1-.beta.-Cytosine arabinoside; Drug: decitabine; Given IV; Other Names: Dacogen; Drug: azacitidine; Given SC; Other Names: 5 AZC; 5-AZC; Drug: 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.; Other Names: Venclexta; ABT-199; ABT199

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite complete remission rate	CR/CRi rate will be determined.	after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR will be determined.	after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
Incidence of adverse events	Safety profile based on NCI CTCAE version 5.0 will be determined.	From the start of treatment until death or last follow-up, assessed for up to 3 years.
measurable residual disease (MRD) negativity	MRD will be assessed by real-time qRCR.	From the start of treatment until death or last follow-up, assessed for up to 3 years.
Impact of concurrent gene mutations	The impact of concurrent gene mutations ( analysis via an 81-gene institutional next-generation sequencing platform) on response and the survival of the combination regimen will be assessed.	Baseline
Overall survival (OS)	OS will be assessed.	From the start of treatment until death or last follow-up, assessed for up to 3 years.
Event-free survival (EFS)	EFS will be assessed.	up to 3 years.
Duration of response (DOR)	DOR will be assessed.	up to 3 years.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Ying Wang, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: venetoclax; acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Decitabine; Cytarabine; Azacitidine; venetoclax; 1-beta-D-arabinofuranosylcytosine 5'-monophosphate
• Other Study ID Numbers: 2023371

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