Clinical trial NCT06429098: Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML
Official title: Study of A Venetoclax-based, Anthracycline-free Regimen in Patients With Newly Diagnosed CBFβ::MYH11-positive Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: venetoclax
acute myeloid leukemia
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-05-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: composite complete remission rate
timeFrame: after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
measure: Incidence of adverse events
timeFrame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
measure: measurable residual disease (MRD) negativity
timeFrame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
measure: Impact of concurrent gene mutations
timeFrame: Baseline
measure: Overall survival (OS)
timeFrame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
measure: Event-free survival (EFS)
timeFrame: up to 3 years.
measure: Duration of response (DOR)
timeFrame: up to 3 years.
Other outcomes:
Locations:
city: Suzhou
country: China
facility: Ethical Committee of the First Affiliated Hospital of Soochow University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Ying Wang
role: PRINCIPAL_INVESTIGATOR
References: