Treatment of Chidamide and Venetoclax for Retinoic Acid and Arsenic Resistant Acute Promyelocytic Leukemia

Официальное название

Multi-center Phase II Prospective Study for the Treatment of Chidamide and Venetoclax in Patients With All-trans Retinoic Acid (ATRA) and Arsenic (As) Resistant Acute Promyelocytic Leukemia (APL)

Обзор

Based on the current treatment with retinoic acid (ATRA) and arsenic (As), most patients with APL achieved long-term survival. There are few patients relapsed and became refractory to the RA and As treatment. In our pre-clinical study, we found that targeting histone deacetylase inhibitor 3 (HDAC3)degraded PML-RARa oncoprotein and induced differentiation and apoptosis of RA and As resistant APL in vitro and in vivo. In this study, we evaluate the efficacy and feasibility of combination therapy for HDAC3 inhibitor and venetoclax in patients with refractory APL.

Подробное описание

For patients with newly-diagnosed acute promyelocytic leukemia (APL), the combination therapy retinoic acid (ATRA) combined with arsenic (As) is the mainstay upfront treatment. Most patients enjoy long-term survival with or without chemotherapy. Even though with such good prognosis, there are still some patients relapsed and eventually became refractory to RA and As treatment. In our pre-clinical study, we demonstrate that targeting histone deacetylase inhibitor 3 (HDAC3) could degrade PML-RARa oncoprotein and induce differentiation and apoptosis of RA and As resistant APL in vitro and in vivo. In this multi-center prospective study, we evaluate the efficacy and feasibility of combination therapy for HDAC3 inhibitor (chidamide) and venetoclax in patients with refractory APL.

Вмешательства

• Препарат Chidamide+venetoclax
  Chidamide 30mg BIW x 4 weeks; Venetoclax 100mg D1, 200mg D2 and 400mg D3-28

Первичные конечные точки

• complete remission and complete remission with incomplete recovery of peripheral blood count [Срок оценки: Day 42]

Вторичные конечные точки (5)

• Overall survival [Срок оценки: 1 year]
• Leukemia-free survival [Срок оценки: 1 year]
• Non-relapse mortality [Срок оценки: 1 year]
• relapse [Срок оценки: 1 year]
• Early death [Срок оценки: 42 days]

Критерии участия

Критерии включения

• Patients with PML-RARα+ APL
• Patients in non-remission status after treatment of RA combined with As
• Patients with life expectance >=3 months
• Inform consent provided

Критерии исключения

• Patients with incontrollable infection
• Patients with life-expectancy less than 2 months
• Patients with abnormal liver (>3XN) and renal function (>3XN）

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• The Affiliated Huai An No 1 Perople's Hospital of NanJing University — Huai'an
• The First Affiliated Hospital of Nanchang University — Nanchang
• Jiong HU — Шанхай
• Zhaxin Hospital, Go Broad Health Care — Шанхай
• NanFang Hospital — Гуанчжоу

Идентификаторы

NCT: NCT05881265 · R/R-APL-2023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗