HVA vs IA/DA or VA in the Treatment of ND HR-AML

Официальное название

The Efficacy and Safety of Homoharringtonine Combined With Venetoclax and Azacitidine Versus Standard Chemotherapy or VA in the Treatment of Acute Myeloid Leukemia With High-risk, a Multicenter, Prospective, Randomized Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат HVA
  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.
• Препарат VA
  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.
• Препарат Standard 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.

Первичные конечные точки

• Composite complete remission (CRc) [Срок оценки: At the end of cycle 2 (each cycle is 28 days).]

Вторичные конечные точки (7)

• Complete remission (CR) [Срок оценки: At the end of cycle 2 (each cycle is 28 days).]
• Overall response rate (ORR) [Срок оценки: At the end of cycle 2 (each cycle is 28 days).]
• DOR [Срок оценки: 1 year]
• Rate of Measurable residual disease (MRD) negative [Срок оценки: At the end of cycle 2 (each cycle is 28 days).]
• Overall survival (OS) [Срок оценки: 1 year]
• Event-free survival (EFS) [Срок оценки: 1 year]
• Adverse events (AE) [Срок оценки: The first dose until 28 days after treatment discontinuation]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Hematology,Nanfang Hospital, Southern Medical University — Гуанчжоу

Идентификаторы

NCT: NCT06810791 · NFEC-2024-576

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗