Newly Diagnosed Acute Myeloid Leukemia With High Risk
Conditions
Keywords
HVA regimen, Intensive chenmotherapy, Fit, randomized controlled trial, Phase 3, VEN combined with AZA, Unfit, Newly diagnosed, High risk, Acute myeloid leukemia
Brief summary
The aim of this study is to evaluate the safety and efficacy of homohartonine combined with venetoclax and azacitidine (HVA) versus intensive chemotherapy (IA/DA) or venetoclax combined with azacitidine (VA) in newly diagnosed high-risk AML patients.
Detailed description
The HVA regimen exerts a synergistic pro-apoptotic effect and has demonstrated significant clinical efficacy against R/R AML and also overcomes adaptive resistance observed in the VA regimen. Exploratory work with small sample sizes in first-line settings suggests that combination of HHT and Ven+AZA exhibits potent anti-AML effects with good safety profiles, particularly in overcoming the impact of high-risk factors associated with AML relative to standard treatments. This indicates its potential as a more ideal option for the treatment of newly diagnosed AML with high risk factors. Therefore a prospective, multi-center, randomized controlled clinical study is planned to evaluate the efficacy and safety of the HVA regimen compared to intensive chemotherapy (IA/DA) or Venetoclax plus azacitidine (VA) regimens in newly diagnosed high-risk fit-AML or unfit AML patients.
Interventions
DRUGHVA
Homoharringtonine (HHT) is given by venous drip daily at 1 mg/m2 from day 1 to 7. Venetoclax (VEN) is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 14. Azacitidine (AZA) is given 75 mg/m2 subcutaneously from day 1 to 7.
DRUGVA
VEN is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 28, and AZA (75 mg/m2) is given subcutaneously from day 1 to 7.
DRUGStandard Chemotherapy
Standard Chemotherapy includes IA(Idarubicin combined with Cytarabine) or DA(Daunorubicin combined with Cytarabine). IDA is given by venous drip daily at 12mg/m2, or DNR is given by venous drip daily at 60mg/m2, from day 1-3, combined with Ara-C at 100mg/m2 by continuously venous drip from day 1-7.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou First People's Hospital
Guangdong Second Provincial General Hospital
Jiangmen Central Hospital
Shenzhen Second People's Hospital
First Affiliated Hospital of Guangxi Medical University
Dongguan People's Hospital
First People's Hospital of Foshan
Guangdong Provincial Hospital of Traditional Chinese Medicine
Huizhou Municipal Central Hospital
Shenzhen Hospital of Southern Medical University
Affiliated Hospital of Guangdong Medical University
People's Hospital of Guangxi Zhuang Autonomous Region
First People's Hospital of Chenzhou
Hunan Provincial People's Hospital
Ganzhou City People's Hospital
First Affiliated Hospital of Gannan Medical University
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with newly diagnosed AML with high risk will be divided into two cohorts, including patients being eligible for intensive chemotherapy and those with unfit status according to Ferrara 2013 criteria. In the fit cohort, patients will be randomized into accepting HVA versus IA/DA for induction with a ratio of 1:1. In the unfit cohort, patients will be randomized into accepting HVA versus VA for induction with a ratio of 1:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* According to the world health organization (WHO) classification of newly diagnosed with AML patients; * Age ≥18 years old; * High-risk patients should meet any of the following criteria: ① High risk group according to the European Leukemia Risk stratification (ELN) 2022; (2) Secondary AML (sAML) which develops from myelodysplastic syndrome (MDS), bone marrow hyperplastic tumor (MPN) or chronic myeloid cell leukemia, et.; (3) Treatment-related AML (t-AML), Patients have a history of cytotoxic treatment record or ionizing radiation therapy. * Patients did not receive anti-AML therapy (except leukopenia therapy, such as hydroxyurea or cytarabine \< 1.0g/d) after the diagnosis of AML; * Expected survival ≥12 weeks; * The eastern tumor cooperation group (ECOG) score 3 points or less; * Kidney function: creatinine clearance acuity 30 ml/min; * Liver function: ALT \< 5 times normal value, bilirubin \< 3 times normal value; * Sign the informed consent form and understand and abide by the plan calls for process.
Exclusion criteria
* Acute promyelocytic leukemia; * With central nervous system leukemia (CNSL) ; * The cardiac function \> level 2; * The AIDS virus (HIV) infection; * Other clinical significance of uncontrolled condition, including but not limited to: (1) out of control, or active systemic infection (viruses, bacteria or fungi); (2) chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; (3) need to actively deal with the merger of the second tumor; * Can't take oral treatment or having a gastrointestinal disease impact ing the absorption; * Being allergy to the experimental drugs; * Pregnant and lactating women; * Patients who could not understand or adhere to the study protocol; * Patients deemed by the investigator to be ineligible for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite complete remission (CRc) | At the end of cycle 2 (each cycle is 28 days). | CRc includes complete remission (CR) and complete remission accompanied with with incomplete count recovery (CRi). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | At the end of cycle 2 (each cycle is 28 days). | ORR includes CRc, partial response (PR), and morphologic leukemia-free state (MLFS). |
| DOR | 1 year | duration of response |
| Rate of Measurable residual disease (MRD) negative | At the end of cycle 2 (each cycle is 28 days). | MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%. |
| Complete remission (CR) | At the end of cycle 2 (each cycle is 28 days). | Complete remission is defined as BM with \>5% blasts and without extramedullary infltration and recovery of peripheral blood cells. |
| Event-free survival (EFS) | 1 year | EFS is calculated from enrollment to the date of relapse or death or the last follow-up. |
| Adverse events (AE) | The first dose until 28 days after treatment discontinuation | AE are recorded from the first dose until 28 days after treatment discontinuation and are graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0. |
| Overall survival (OS) | 1 year | OS is calculated from enrollment to death or the last follow-up. |
Countries
China
Contacts
Primary ContactGuopan Yu
Outcome results
None listed