Phase II Study of (Early) Combination Salvage Therapy With Venetoclax and Intensified Decitabine in Relapsed/Refractory AML
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Rate of hematological remissions
研究概览
简要总结
The goal of this prospective, phase II single center, one arm, open label clinical trial is to test the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in patients with newly diagnosed AML (acute myeloid leukemia) and primary induction failure and patients with relapse of AML/MDS IB2 (myelodysplastic neoplasm with increased blasts 2) after chemotherapy. The primary endpoint is hematologic remission after treatment with Decitabine and Venetoclax. Participants eligible for the trial will receive a treatment of ten days of Decitabine and twenty-eight days of Venetoclax for one or two cycles, after which hematological remission will be assessed. Follow up will include the first one hundred days after end of treatment.
详细描述
This is a prospective, phase II single center one arm, open label clinical trial testing the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in relapsed or refractory AML and MDS IB2. Enrolled will be twenty-seven patients with newly diagnosed AML and primary induction failure to conventional anthracycline-based induction chemotherapy, as well as patients with a relapse of AML oder MDS IB2 after chemotherapy. Patients will receive a combination therapy of ten days of Decitabine and twenty-eigt days of Venetoclax. If hematologic remission is not achieved after one cycle of treatment, patients receive a second cycle. After treatment, a follow-up period of 100 days will ensue. The main aim of the trial is the assessment of hematologic remission after combining Venetoclax with a time-dense immediate application of the hypomethylating agent Decitabine after failure of a chemotherapy approach, thus additionally altering backbone treatment modalities from chemotherapy to epigenetic and anti-BCL2 (B-cell lymphoma 2) treatment. A first assessment of safety and feasibility will take place after the treatment of three patients and a second assessment for safety, feasibility and efficacy/futility after nine patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment
Salvage therapy with Venetoclax and intensified Decitabine
干预措施: Decitabine (Drug)
Treatment
Salvage therapy with Venetoclax and intensified Decitabine
干预措施: Venetoclax (Drug)
结局指标
主要结局
Rate of hematological remissions
时间窗: measured after the first and second cycle (each cycle is 28 days)
Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology\*) after one or two cycles of Decitabine/Venetoclax. \* or bone marrow pathology, if aspiration morphology not available, not representative or not judged sufficiently reliable by treating physician
次要结局
- Overall survival(day 100 after end of treatment)
- Early Mortality(day 30 after start of treatment)
- Rate of CTCAEs ≥ Grade 3(observed during the first and second cycle (each cycle is 28 days) and until day 30 after therapy application)
- Time to hematopoietic recovery in days(after each chemotherapy treatment cycle (28 days), defined as the time from the start of the cycle until recovery)
- Rate of MRD-negativity (measurable residual disease)(measured at each remission assessment (C1D15, C1D28, C2D28, Follow Up))
- Rate of infectious complications CTCAEs ≥ grade 3(measured during the first and second cycle and the first 30 days after end of treatment (each cycle is 28 days))
- Time to transplant in days(until day 100 after end of treatment)
- Progression-free survival(day 100 after end of treatment)
- Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30))(at screening and at the end of cycle one and two (one cycle is 28 days) and at follow up (day 100 after end of treatment))
- Hospitalisation days(Day 1 of therapy until day 30 after end of treatment)
- ECOG prior to start of conditioning for transplant(between end of treatment and follow up)