Exploratory Study of Venetoclax, Homoharringtonine, Azacitidine Plus G-CSF for Newly Diagnosed AML (VHAG)

Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFirst People's Hospital of Hangzhou

About this trial

This study is a single-arm, prospective, multi-center exploratory clinical trial. A total of 61 patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable for intensive chemotherapy will be enrolled. The Simon two-stage design will be adopted to control the type I and type II errors, with the minimum acceptable composite remission rate of 65% and a power of 80%.

Prior to treatment, subjects will undergo screening within 28 days, including bone marrow aspiration, genetic testing, ECOG performance status assessment, and organ function evaluation. Data will be recorded in Excel and subject to unified quality control. During the treatment period, G-CSF (granulocyte colony-stimulating factor) will be administered subcutaneously as appropriate, and supportive care such as antiemetic and hydration therapy will be provided routinely.

For patients who achieve remission, individualized consolidation therapy will be given: those eligible for transplantation will undergo allogeneic hematopoietic stem cell transplantation; those who can tolerate moderate-intensity treatment will receive consolidation with medium-dose cytarabine first, followed by 4 cycles of VHAG regimen consolidation. Patients with FLT3 mutations will receive additional targeted therapy during consolidation.

Safety assessment will be conducted in accordance with the NCI-CTCAE Version 5.0. For grade 4 hematological toxicity or severe non-hematological toxicity, the treatment dose will be adjusted or the treatment will be suspended. Severe adverse events will be reported in a timely manner, and all research-related data will be retained for at least 10 years in accordance with relevant regulations.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

The patient has fully understood the study, voluntarily participated, and signed the informed consent form (ICF).

Newly diagnosed acute myeloid leukemia (AML) confirmed by bone marrow morphology, immunophenotyping, cytogenetics, and/or molecular biology testing, in accordance with the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2022 edition).

No prior systemic therapy for AML (including induction, consolidation, or maintenance therapy).

Patients judged unfit for standard cytarabine plus anthracycline induction chemotherapy due to age or comorbidities.

Disqualifiers

Acute promyelocytic leukemia (APL).

History of prior myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, myelofibrosis, etc.

Prior receipt of hypomethylating agents, venetoclax (VEN), or systemic chemotherapy for myelodysplastic syndromes (MDS).

Prior receipt of any investigational drug or device therapy for MDS/AML.

Trial design

Design model

Single group

Treatments tested in this trial

  • Intervention for Venetoclax

    Drug

    Oral administration of venetoclax. The starting dose is 100 mg on Day 2, 200 mg on Day 3, and 400 mg once daily from Day 4 to Day 10 of each induction cycle. Dose adjustments may be made per protocol based on tolerability and safety.

  • Intervention for Homoharringtonine

    Drug

    Intravenous infusion of homoharringtonine at a dose of 1 mg/m² daily from Day 1 to Day 7 of each induction cycle.

  • Intervention for Azacitidine

    Drug

    Subcutaneous or intravenous administration of azacitidine at a dose of 75 mg/m² daily from Day 1 to Day 7 of each induction cycle.

  • Intervention for G-CSF

    Drug

    Subcutaneous administration of G-CSF at a dose of 5 μg/kg daily, initiated prior to the start of induction therapy (Day 0). Discontinuation will be per protocol when the white blood cell count (WBC) exceeds 30 × 10⁹/L.

Treatment groups

61 Participants
are divided into 1 treatment group
Group A: VHAG Regimen Treatment ArmExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

CRc(CR+CRi)

Composite complete remission (CR) plus CR with incomplete hematologic recovery

Time frame
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Secondary outcomes

1

ORR(CR+CRi+MLFS+PR)

Objective Response Rate (Complete Response + Complete Response with incomplete hematologic recovery + Marrow Leukemia-Free State + Partial Response)

Time frame
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
2

OS

Overall Survival

Time frame
1year
3

RFS

Relapse-Free Survival

Time frame
1year
4

MRD

Rate of negative conversion of evaluable minimal residual disease (MRD)

Time frame
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Other outcomes

1

EBS

Exploratory biomarker assessment

Time frame
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

First People's Hospital of Hangzhou

Lead sponsor

The Affiliated People's Hospital of Ningbo University

Collaborator

Zhejiang University

Collaborator

The Central Hospital of Lishui City

Collaborator

Jinhua Central Hospital

Collaborator

Shaoxing People's Hospital

Collaborator

Shaoxing Second Hospital

Collaborator

Jinhua People's Hospital

Collaborator

Dongyang People's Hospital

Collaborator

Taizhou Hospital

Collaborator

Huzhou Central Hospital

Collaborator

Affiliated Hospital of Jiaxing University

Collaborator

The Second Affiliated Hospital of Jiaxing University

Collaborator

Second Affiliated Hospital of Wenzhou Medical University

Collaborator

Ningbo Medical Center Lihuili Hospital

Collaborator

Yuyao People's Hospital

Collaborator

Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

Collaborator

Zhejiang Provincial Tongde Hospital

Collaborator

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