A Single-arm, Pilot Study of Venetoclax in Combination With 5 Days Azacitidine in Treatment-naïve Subjects With Acute Myelogenous Leukemia Who Are ≥18 Years of Age and Not Eligible for Standard Induction Therapy (VENAZA-5S PILOT TRIAL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 45
- 试验地点
- 20
- 主要终点
- The primary outcome measure is the response rate defined as the rate of CR/CRi after up to 6 cycles of therapy (best response).
研究概览
简要总结
Acute myeloid leukemia (AML): continuous oral Venetoclax (VEN) and 7 days of s.c. Azacitidine (AZA) per 28-day cycle = standard of care for intensive induction therapy ineligible AML patients in Germany
The VENAZA-5S pilot trial: AZA administration reduced to 5 days within each cycle to improve tolerability and treatment adherence due to less neutropenic infections, less treatment interruptions and less hospitalizations.
详细描述
Acute myeloid leukemia (AML) is a uniformly fatal disease if untreated. The combination of continuous oral Venetoclax (VEN) and 7 days of s.c. Azacitidine (AZA) per 28-day cycle has recently emerged as the new standard of care for AML patient who are ineligible for intensive induction therapy, and has been widely adopted in Germany.
The VENAZA-5S pilot trial aims to reduce the reported hematological toxicity profile of this currently approved combination, while preserving efficacy, by modifying AZA administration to 5 days within each cycle. The hypothesis is that this modification will not interfere with the response rates achieved by the combination, but will rather improve tolerability and treatment adherence due to less neutropenic infections, less treatment interruptions and hospitalizations, and thus result in better quality of life and favorable long-term outcomes in elderly or comorbid AML patients. This single-arm pilot study is intended to generate first data on the efficacy and toxicity of 5 days AZA + VEN, which will be compared to a historical control cohort treated with the current standard of 7 days AZA + VEN.
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
- •Confirmed diagnosis of AML by World Health Organization (WHO) criteria 2016
- •Ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or comorbidities
- •Age ≥ 18 years
- •Life expectancy of at least 12 weeks
排除标准
- •Prior treatment for AML or myelodysplastic syndrome (MDS) with one of the following:
- •Hypomethylating agent (HMA)
- •Chemotherapeutic agent
- •Chimeric Antigen Receptor (CAR)-T cell therapy
- •Experimental therapies
- •Note: Prior use of hydroxyurea is allowed
- •History of myeloproliferative neoplasm (MPN)
- •Diagnosis of acute promyelocytic leukemia (APL)
- •Presence of favorable-risk karyotype abnormalities: t(15;17), t(8;21), inv(16) or t(16;16)
研究组 & 干预措施
VEN+AZA-5
Azacitidine (AZA) 75 mg/m2, d1-5 of each 28 day cycle (SC) in combination with Venetoclax (VEN): 400 mg daily (orally)
干预措施: VEN+AZA-5 (Drug)
结局指标
主要结局
The primary outcome measure is the response rate defined as the rate of CR/CRi after up to 6 cycles of therapy (best response).
时间窗: best response after up to 6 cycles (each cycle is 28 days)
Bone marrow assessments will be performed at least at screening, at the end of cycle 1, after cycle 4 and after cycle 6 resp. end of treatment (EOT). Criteria for disease status / response assessment follow the ELN-2022 recommendations .
次要结局
- Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy(after up to 6 cycles (each cycle is 28 days))
- Objective response rate(at EOT, after up to 6 cycles therapy (each cycle is 28 days))
- Rate of patients with at least one treatment interruption(From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days)))
- Duration of patient hospitalization(From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days)))
- Time from initiation of treatment (C1D1) until achievement of CR or CRi(from start of treatment (C1D1) until up to 6 cycles (each cycle is 28 days))
- Quality of life (QoL)(From Screening until EOT (after up to 6 cycles (each cycle is 28 days)))
- Event free survival (EFS)(From start of treatment to the date of relapse from CR or CRi, treatment failure (i.e., no CR or CRi after up to 6 cycles (each cycle is 28 days) of therapy or disease progression requiring treatment discontinuation), or death from any cause.)
- Overall survival (OS)(From start of treatment to date of death from any cause. OS will be assessed until 3 months after end of treatment of the last patient on study.)
- Descriptive assessment of measurable residual disease (MRD) levels on study treatment, determined by quantitative PCR or targeted next-generation sequencing(From Screening until EOT (after up to 6 cycles (each cycle is 28 days)))
- Time to treatment discontinuation(From start of treatment to day of treatment discontinuation (within up to 6 cycles (each cycle is 28 days)))
- Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration(From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days)))
- Rate of CR or CRi by the Initiation of Cycle 2(At the end of Cycle 1 (each cycle is 28 days))
研究者
Klaus Metzeler
Prof. Dr. med. Klaus Metzeler
University of Leipzig