Newly Diagnosed Mixed Phenotype Acute Leukemia (MPAL)
Conditions
Keywords
Mixed Phenotype Acute Leukemia(MPAL), homoharringtonine, venetoclax
Brief summary
This study aims to evaluate the safety and efficacy of homoharringtonine combined with venetoclax and azacitidine regimen (HVA) in newly diagnosed MPAL patients, providing a basis for the use of the HVA regimen in the treatment of MPAL.
Detailed description
Our preliminary studies show that MPAL not only highly expresses BCL-2, but also highly expresses MCL-1, suggesting the need to explore combining MCL-1 inhibitors on the basis of Ven and HMAs. Our preliminary research confirmed that homoharringtonine (HHT) significantly enhances the anti-leukemia effect of Ven/AZA via inhibition of MCL-1. Originally, we designed the HVA regimen by combining HHT with Ven/AZA for the treatment of AML, and achieved better efficacy and safety. Then we exploratively treated 11 MPAL patients with HVA regimen and acquired promising response and safety. In this study, we conduct a multicenter, prospective, single arm trial to evaluate the efficacy and safety of HVA in the treatment of newly diagnosed MPAL.
Interventions
DRUGHVA
HVA regimen: Venetoclax: 100 mg on day 1, 200 mg on Day 2, 400 mg per day from Day 3 to Day 14; Azacitidine: 75 mg/m2 per day by subcutaneous injection from Day 1 to Day 7; Homoharringtonine : 1mg/m2 per day by intravenous infusion from Day 1 to Day 7. If co-administered with CYP3A inhibitors, the dose of venetoclax was adjusted in accordance with prescribing recommendations. Fms-related receptor tyrosine kinase 3 (FLT3) inhibitors were recommended in patients with FLT3-ITD/TKD mutations. Also tyrosine kinase inhibitors were recommended in patients with BCR/ABL-positive.
Sponsors
Guangdong Second Provincial General Hospital
Nanfang Hospital, Southern Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First Affiliated Hospital of Guangxi Medical University
Guangzhou First People's Hospital
Zhongshan People's Hospital, Guangdong, China
Dongguan People's Hospital
Shenzhen Second People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
If there are other parties who are masked in the clinical trial besides those listed above, use this space to describe those parties.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient fully understands this study, voluntarily participates, and signs the informed consent form (ICF); 2. Age ≥18 years; 3. Newly diagnosed with MPAL according to the World Health Organization (WHO) 2022 classification. 4. The patient has not started anti-leukemia treatment after the initial diagnosis (except cytoreductive therapy, such as hydroxyurea or cytarabine \<1.0 g/day or glucocorticoids); 5. Expected survival ≥12 weeks; 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2; 7. Normal cardiac function, left ventricular ejection fraction ≥50%; normal renal function: creatinine clearance ≥30 ml/min; normal liver function: ALT \<5 times the normal value, bilirubin \<3 times the normal value;
Exclusion criteria
1. Patients who have had or currently have other malignant tumors requiring treatment; 2. Patients with central nervous system (CNS) infiltration; 3. Other clinically significant uncontrolled conditions, including but not limited to: (1) uncontrolled or active systemic infections (viral, bacterial, or fungal); (2) chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; (3) uncontrolled hypertension, etc.; 4. Patients who cannot take oral medications or have malabsorption syndrome; 5. Patients with a known history of immediate or delayed hypersensitivity reactions to drugs of the same class as the study medication or to excipients; 6. Pregnant or breastfeeding women, or patients who refuse to use effective contraception during the study; 7. Patients with a history of severe neurological or psychiatric disorders who cannot understand or comply with the study protocol; 8. Patients with severe heart disease, such as myocardial infarction, severe or unstable angina, severe arrhythmias; 9. Patients known to be infected with human immunodeficiency virus (HIV); patients with active hepatitis B or C; subjects who are inactive hepatitis carriers or whose viral hepatitis titers are low after treatment with non-prohibited antiviral drugs are not excluded; 10. Patients who cannot take oral medications or have malabsorption syndrome; 11. Patients whom the investigator determines are unsuitable to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete Remission (CRc) | At the end of cycle 2 (28 days for a cycle) | The rate of composite complete remission including complete remission (CR) and CR with incomplete blood count recovery (CRi) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission (CR) | At the end of cycle 2 (28 days for a cycle) | Camplete remission is defined as BM with\>5% blasts and wthout extramedullary infltration and recovery of peripheral blood cells. |
| Overall response rate (ORR) | At the end of cycle 2 (28 days for a cycle) | ORR includes CRc, partial response (PR), and morphologic leukemia-free state(MLFS). |
| Rate of Measurable residual disease (MRD) negative | At the end of cycle 2 (28 days for a cycle) | MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%. |
| Adverse events | At the end of cycle 2 (28 days for a cycle) | Adverse events including hematologic and nonhematologic toxicities in the treatment of HVA regimen |
Countries
China
Outcome results
None listed