HVA in the Treatment of Mixed-Phenotype Acute Leukemia(MPAL). (HVA-MPAL)

The Efficacy and Safety of Homoharringtonine Combined With Venetoclax and Azacitidine (HVA) in the Treatment of Mixed-Phenotype Acute Leukemia (MPAL), a Multicenter, Prospective, Single-arm Trial

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Newly Diagnosed Mixed Phenotype Acute Leukemia (MPAL)
• Intervention / Treatment: Drug: HVA

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Department of Hematology, Guangdong Second Provincial General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HVA regiment; HVA regiment for newly diagnosed MPAL

Drug: HVA; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Remission (CRc)	The rate of composite complete remission including complete remission (CR) and CR with incomplete blood count recovery (CRi)	At the end of cycle 2 (28 days for a cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR)	Camplete remission is defined as BM with>5% blasts and wthout extramedullary infltration and recovery of peripheral blood cells.	At the end of cycle 2 (28 days for a cycle)
Overall response rate (ORR)	ORR includes CRc, partial response (PR), and morphologic leukemia-free state(MLFS).	At the end of cycle 2 (28 days for a cycle)
Rate of Measurable residual disease (MRD) negative	MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%.	At the end of cycle 2 (28 days for a cycle)
Adverse events	Adverse events including hematologic and nonhematologic toxicities in the treatment of HVA regimen	At the end of cycle 2 (28 days for a cycle)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is calculated from enrollment to death or the last follow-up.	1 year
Relapse-Free Survival (RFS)	The time from the beginning of the implementation of the mitigation measures to the occurrence of disease progression, any cause of death, or the last follow-up visit	1 year
Duration of Response (DOR)	It refers to the period from when the patient achieves CR/CRi until the patient loses CR/CRi.	1 years

Collaborators and Investigators

• Sponsor: Guangdong Second Provincial General Hospital
• Collaborators: Guangzhou First People's Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Shenzhen Second People's Hospital; Dongguan People's Hospital; Zhongshan People's Hospital, Guangdong, China; First Affiliated Hospital of Guangxi Medical University; Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: venetoclax; homoharringtonine; Mixed Phenotype Acute Leukemia(MPAL)
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Biphenotypic, Acute
• Other Study ID Numbers: GD2H-2026-571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No