AML (Acute Myeloid Leukemia)
Conditions
Keywords
AML, Venetoclax, chemotherapy, BCL2 inhibitor
Brief summary
This is a multicenter, prospective, single-arm clinical study designed to evaluate the efficacy and safety of the VA-CIG regimen (venetoclax combined with azacitidine, idarubicin, low-dose cytarabine and granulocyte colony-stimulating factor \[G-CSF\]) as induction therapy for previously untreated patients with fit acute myeloid leukemia (AML) who are eligible for intensive chemotherapy. This study aims to evaluate the efficacy and safety of the VA-CIG regimen in the target patient population.
Interventions
DRUGVenetoclax, Azacitidine, Cytarabine, Idarubicin, G-CSF
* Venetoclax: 100 mg on Day 1, 200 mg on Day 2, 400 mg on Day 3, and 400 mg on Days 4-14, orally, once daily; * Azacitidine: 75 mg/m²/d, subcutaneous injection, on Days 1-7; * Cytarabine: 100 mg/m²/d, intravenous infusion, on Days 1-5; * Idarubicin: 6 mg/m²/d, intravenous infusion, on Days 1-3; * Human granulocyte colony-stimulating factor (G-CSF): 200 μg/m²/d, subcutaneous injection, from Day 0 until the white blood cell count \> 10×10⁹/L. One cycle lasts for 28 days
Sponsors
Beijing 302 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of acute myeloid leukemia (AML, excluding acute promyelocytic leukemia) confirmed by morphology, immunophenotyping and molecular genetics, in accordance with the WHO 2022 diagnostic criteria for AML; * Age 18-70 years, with no gender restriction; * No prior AML-related treatment has been received; exceptions are made for the use of hydroxyurea or similar agents during the diagnostic screening phase to control peripheral blood leukemic blasts; * Patients must be assessed as tolerable to intensive chemotherapy regimens; evaluation of tolerance to intensive chemotherapy shall be performed in accordance with the Ferrara 2013 criteria (Appendix A); * Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2; * Serum creatinine ≤ 2.0 × upper limit of normal (ULN), or creatinine clearance \> 40 mL/min calculated by the Cockcroft-Gault formula for glomerular filtration rate (GFR); * Total bilirubin ≤ 2 × ULN, and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 × ULN; * Left ventricular ejection fraction (LVEF) ≥ 45%, or LVEF measured by echocardiography (ECHO) within the normal range; * Expected survival \> 3 months.
Exclusion criteria
* Subjects with a history of myeloproliferative neoplasms (MPNs), including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, and acute myeloid leukemia (AML) with BCR-ABL1 translocation; * Patients with a prior history of venetoclax or azacitidine (Aza) treatment for other diseases; * Known hypersensitivity to any component of the investigational medicinal products; * History of other concurrent malignancies within 2 years prior to enrollment, except: Adequately treated carcinoma in situ of the cervix or breast; Basal cell carcinoma or localized squamous cell carcinoma of the skin; Previously controlled malignancies treated with radical surgical resection (or other curative modalities), etc. * Presence of uncontrolled severe infection or active bleeding; * Pregnant or lactating women; * Subjects with active, treatment-uncontrolled viral infection caused by HIV, hepatitis B virus, or hepatitis C virus; * Subjects with evidence of central nervous system leukemia before treatment initiation; * Women of childbearing potential who do not agree to use at least one reliable contraceptive method from Day 1 of the study until 90 days after the last dose of study medication; sexually active male subjects who do not agree to use contraceptive measures from Day 1 of the study until 90 days after the last dose of study medication; male subjects who do not agree to refrain from sperm donation from the start of study drug administration until at least 90 days after the last dose; * Subjects with epilepsy requiring pharmacotherapy, dementia, or other abnormal psychiatric conditions that impair the ability to understand or comply with the study protocol; * Presence of psychiatric disorders or cognitive impairment that prevents cooperation with treatment and follow-up; conditions limiting oral drug intake or gastrointestinal absorption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite complete response rate (CR+CRi) | At the end of Cycle 1 (each cycle is 28 days) | CR is defined as: following two cycles of induction therapy, a blast count of \< 5% in the bone marrow, absence of Auer rods, no evidence of extramedullary leukemia, and peripheral blood absolute neutrophil count (ANC) and platelet count of \> 1×10⁹/L and \> 100×10⁹/L, respectively. CRi is defined as: fulfilling all criteria for CR, except for a persistent absolute neutrophil count (ANC) \< 1×10⁹/L or a persistent platelet count \< 100×10⁹/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRD remission rate | At the end of Cycle 1 (each cycle is 28 days) | Defined as: the number of patients who achieved MRD-negative status after induction therapy / the total number of patients who underwent MRD testing at that time point × 100%; MRD-negative is defined as an MRD level \< 10-⁴ in bone marrow samples; |
| Adverse events | Start of treatment to 2 weeks after end of treatment | Number of subjects with each adverse event. |
Countries
China
Contacts
CONTACTDr. Gao Xiaoning, Chief Physician, Professor
Outcome results
None listed