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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06429098
• Other study ID #: 2023371
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: December 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Ying Wang
• Phone: 008613656214782
• Email: wangying77[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults = 18 years.

2. Newly diagnosed CBFß::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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• azacitidine
Given SC
• decitabine
Given IV
• Cytarabine
Given IV

Locations

Country	Name	City	State
China	Ethical Committee of the First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate (ORR)	ORR will be determined.	after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
Secondary	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.
Secondary	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.
Secondary	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
Secondary	Overall survival (OS)	OS will be assessed.	From the start of treatment until death or last follow-up, assessed for up to 3 years.
Secondary	Event-free survival (EFS)	EFS will be assessed.	up to 3 years.
Secondary	Duration of response (DOR)	DOR will be assessed.	up to 3 years.