Phase II Study on Venetoclax (VEN) Plus Decitabine (DEC) (VEN-DEC) for Elderly (≥60 <75years) Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Elegible for Allogeneic Stem Cell Transplantation (allo-SCT)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 25
- 主要终点
- Allo-SCT
研究概览
简要总结
This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the safety and efficacy of the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) as "bridge" to allo-SCT in elderly (≥ 60 - < 75 years) AML patients. The primary objective is to evaluate the proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/Cri/MLFS.
详细描述
This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS, organized under the auspices of the Gruppo Italiano TRapianti di Midollo Osseo (GITMO) that involves the prinicipla centres active in transplantation of any kind of stem cells in Italy. The target for this study is 100 patients.
Biologic characterization of AML will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR on target genes (FLT3, NPM1A, WT1,) at disease onset. MRD monitoring will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR (routine assessment) at the time of CR/CRi/MLFS before allo-SCT and during follow up (at least 4 timepoints: +100 days, +180 days, +1 year and +2 years from allo-SCT).
Genomic analysis by NGS gene-panel (Sophia Genetics) exploring the mutational status of the genes involved in of AML will be centralized in Brescia Laboratory at the enrollment into the study (diagnosis) and at the time of no response (PR/NR), before allo-SCT in patients in CR/CRi/MLFS and in case of relapse, at any time.
Primary Objectives To evaluate the proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML eligible for allo-SCT treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS.
Secondary Objectives
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
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Patients >60 <75 years of age
- •Diagnosis of AML eligible for allo-SCT from any donor
- •High- and Intermediate-Risk ELN
- •WBC <25x109/L (Hydroxyurea is permitted to meet this criterion)
- •adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL)
- •adequate renal function (creatinine clearance ≥50 ml/min)
- •ECOG Performance Status < 2
- •Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial.
- •Women of childbearing potential must use highly effective contraception for at least 1 month after the last dose of VEN and for however long the EU SmPC says for DEC
- •Willing and able to comply with all of the requirements and visits in the protocol.
- •Written and signed informed consent.
排除标准
- •• Previous treatment for AML (Hydroxyurea is allowed) or for an antecedent Myelodysplastic Syndrome (MDS).
- •Absence of informed consent
- •AML patients with t(15;17); t(8;21); inv(16)
- •Subject has known active CNS involvement with AML.
- •Low Risk ELN
- •grade >2 NCI-CTCAE (v. 5) adverse events at the time of enrollment
- •Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) <40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min.
- •The evidence of HBV or HCV active infection (HBV DNA HCV RNA positive test).
- •Patients with HIV infection
- •Current uncontrolled infections
- •Patients with other life-threatening concurrent disease
- •Subjects with known hypersensitivity to any of the component medication
- •Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:
- •Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
- •Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- •Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. • Participation in another clinical trial within 1 month before the start of this trial
研究组 & 干预措施
Treatment with VEN-DEC
Venetoclax will be given with a 3-day ramp up beginning with 100 mg dose on Day 1, with 200mg on Day 2, to reach the final dose of 400 mg on Day 3 of Cycle 1. Venetoclax will be continued at 400 mg daily. Tumor lysis prophylaxis will be administered from day -4, cycle 1 (oral uric acid reducing agent and hydration with at least 1.5 L/day).Decitabine will be administered at the dose of 20 mg/sqm intravenously from day 1 to day 5 every 28 days (VEN-DEC) for 2 cycles.
干预措施: Venetoclax and Decitabine (Combination Product)
结局指标
主要结局
Allo-SCT
时间窗: 18 months from 1st enrolled patient
Proportion of patients who undergo to allo-SCT in first CR/CRi/MLFS
Allo-SCT Engraftment
时间窗: up to 24 weeks
Percentage of patients with Neutrophil engraftment and percentage of patients with platelet engraftment
Response to VEN-DEC chemo-free combination (ELN Guidelines)
时间窗: At the end of cycle 2 (each cycle is 28 days)
response to VEN-DEC induction will be assessed on bone marrow according to the ELN Guidelines (13), as following: - CR without minimal residual disease (CR-MRD neg); (Complete Remission ) bone marrow blasts 5%) - CR remission with incomplete hematologic recovery (CRi): Morphologic Leukemia-free State (MLFS) Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%; - Primary refractory disease/Non response (NR): No CR or CRi after 2 courses of VEN-DEC; excluding patients with death in aplasia or death due to indeterminate cause;
Cumulative incidence of Non-Relapse Mortality
时间窗: at 365 days
NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 365 days
Overall Survival (OS)
时间窗: at 2 year post transplant
at 2 year post transplant. OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis
Cumulative incidence of Non-Relapse Mortality
时间窗: at 100 days
NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 100 days
Cumulative incidence of Non-Relapse Mortality
时间窗: at 180 days
NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 180 days
次要结局
未报告次要终点