2023-510432-36-00招募中2 期
A MULTICENTRIC PHASE 2 STUDY OF VENETOCLAX AND AZACITIDINE FOR THE MANAGEMENT OF MOLECULAR RELAPSE/PROGRESSION IN ADULT NPM1-MUTATED ACUTE MYELOID LEUKEMIA. AML2521
Fondazione Gimema Franco Mandelli Onlus29 个研究点 分布在 1 个国家目标入组 35 人开始时间: 2024年7月4日最近更新:
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 29
- 主要终点
- Percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant
研究概览
简要总结
The primary objective of the trial is to determine the efficacy of venetoclax and azacitidine in preventing morphological relapse in adult NPM1mut AML patients who experience molecular relapse/progression during chemotherapy treatment or subsequent follow-up monitoring.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Subject must be greater than or equal to 18 years of age
- •Female subjects of childbearing potential must have negative results for pregnancy test at screening
- •Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from screening through 3 months after the end of treatment.
- •Signed written informed consent according to ICH/EU/GCP and national local laws.
- •Subject must have received previous diagnosis of NPM1mut AML with or without concomitant FLT3-TKD or FLT3-ITD
- •At screening, subject must have confirmed NPM1 type A, B, or D mutant transcripts
- •Subject must be eligible for alloSCT, according to transplant center policy
- •Subject must have undergone at least two cycles of conventional anthracycline- and cytarabine based chemotherapy, achieving first CR (CR1)
- •Subject must be in morphological CR1 with bone marrow detectable minimal residual disease (MRD) positivity, defined as qRT-PCR NPM1 transcript = 0.01/100 ABL1 copies and confirmed in two consecutive determinations performed at 2 to 4 weeks’ distance: a. Molecular progression is defined in patients with molecular persistence at low copy number as an increase of MRD copy number = 1 log10 between 2 positive samples. b. Molecular relapse is defined in patients previously tested MRD negative as an increase in MRD copy number = 1 log10 between 2 positive samples
- •Subject must have a projected life expectancy of at least 12 weeks.
- •Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status < 2
- •Subject must have adequate renal and hepatic function per local laboratory reference range as follows: - Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0X ULN - Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of nonhepatic origin) - Subject must have adequate renal function as demonstrated by a creatinine clearance = 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours’urine collection.
排除标准
- •Subject has acute promyelocytic leukemia (APL)
- •Creatinine clearance < 30 ml/min
- •Subject has a cardiovascular disability status of New York Heart Association Class > 2 a. Class 2 is i. defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity ii. results in fatigue, palpitations, dyspnea, or anginal pain
- •Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post-menopausal women must be amenorrhoic for at least 12 months to be considered of non-child bearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs.
- •Patients unwilling or unable to comply with the protocol
- •Subject has known active CNS involvement with AML
- •Subject has received previous treatment with venetoclax and/or hypomethylating agents
- •Subject has undergone alloSCT for AML
- •Subject has more than 5% of bone marrow blast cells at screening bone marrow aspirate
- •Subject is known to be positive for HIV
- •Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) b. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
- •Cardiac history of CHF requiring treatment or Ejection Fraction = 50% or chronic stable angina;
- •DLCO = 65% or FEV1 = 65%;
结局指标
主要结局
Percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant
Percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant
次要结局
- MRD negativity rate at 3 and 6 months and at transplant
- Percentage of patients undergoing alloSCT in CR
- Percentage of patients undergoing alloSCT in MRD negativity
- Disease Progression rate at 3, 6 and 12 months and at transplant
- Molecular Disease Progression at 3, 6 and 12 months and at transplant
- Overall Survival (OS), defined as the number of days between the first study drug administration and death from any cause or lost to follow up.
- Progression-Free Survival (PFS), defined as the number of days between the first study drug administration and any event including disease progression or death.
- Molecular Disease-Free Survival (MDFS), defined as the number of days between the data of response (MRD negativity) and molecular disease progression or death.
- Molecular progression-free survival (MPFS), defined as the number of days between the first study drug administration and molecular disease progression or death.
- Safety and toxicity of venetoclax-azacitidine in the experimental setting
研究者
GIMEMA Centro Dati
Scientific
Fondazione Gimema Franco Mandelli Onlus
研究点 (29)
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