2023-505379-61-00招募中2 期
HOVON 171 AML: A single arm phase II trial to assess cobicistat boosted venetoclax in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (AML) who are not considered candidates for intensive treatment regimens
Haemato Oncology Foundation For Adults Netherlands19 个研究点 分布在 1 个国家目标入组 142 人开始时间: 2023年10月25日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 142
- 试验地点
- 19
- 主要终点
- Run-in phase: Pharmacokinetic equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).
研究概览
简要总结
Run-in phase: To evaluate the pharmacokinetic (PK) equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2). Extentension phase: To assess the practical applicability and the therapeutic effect of a defined schedule of cobicistat added to venetoclax and azacitidine (AZA/VEN/COBI) on overall survival (OS) in adult patients with newly diagnosed AML considered ineligible for intensive chemotherapy.
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
- •Patients with: a diagnosis of AML and related precursor neoplasms according to ICC-2022 classification (excluding acute promyelocytic leukaemia). Patients may have had previous treatment with erythropoiesis stimulating agents (ESA) for an antecedent phase of MDS. ESAs must be stopped at least two weeks before registration.
- •Patients 18 years and older who are considered not fit for intensive chemotherapy (judged by treating physician) or who decline the option of intensive chemotherapy.
- •WHO performance status 0, 1 or
- •Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: 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. Serum bilirubin ≤ 3 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert’s syndrome. Alanine transaminase (ALT) ≤ 3 x ULN, unless considered AML-related.
- •Male subjects who are sexually active, must agree, from Study Day 1 until at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
- •Female subjects must be either postmenopausal defined as: Age >55 years with no menses for ≥12 months, without an alternative medical cause. OR willing and able to use adequate contraception during and until 180 days after the last protocol treatment.
- •Written informed consent.
- •Patient is capable of giving informed consent.
- •Patient agrees not to participate in another interventional study while on protocol treatment without approval of the (co-) Principal Investigator.
排除标准
- •Acute promyelocytic leukemia.
- •History of non-compliance to medical regimens or considered unreliable with respect to compliance.
- •Senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
- •Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea.
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- •Unreplaceable use of strong inhibitors or inducers of CYP3A or CYP3A/p-GP substrates with a narrow therapeutic window (e.g., cobicistat or ritonavir for HIV treatment).
- •Intolerability, contra-indication or allergy to one of the study drugs.
- •Exclusion for the run-in phase only: Patient with a strong indication for IFD prophylaxis (or treatment)
- •Myelodysplastic syndrome (MDS).
- •Patients previously treated for AML or MDS (any anti-leukemic therapy including investigational agents; excluding: 1) erythropoiesis stimulating agents (ESAs); 2) hydroxyurea (hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis).
- •Diagnosis of any previous or concomitant malignancy is an exclusion criterion: except when the patient successfully completed treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 24 months prior to registration; except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
- •Blast crisis of chronic myeloid leukemia.
- •Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.).
- •Cardiac dysfunction as defined by: Myocardial infarction within the last 3 months of study entry; or reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram; or unstable angina or New York Heart Association (NYHA) grade IV congestive heart failure; or unstable cardiac arrhythmias.
- •History of stroke or intracranial haemorrhage within 6 months prior to registration.
- •Symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement).
结局指标
主要结局
Run-in phase: Pharmacokinetic equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).
Run-in phase: Pharmacokinetic equivalence of cobicistat boosted venetoclax and unboosted venetoclax (PK cycle 1 vs PK cycle 2).
Extension phase: Overall survival (OS)
Extension phase: Overall survival (OS)
次要结局
- Run-in phase: Venetoclax and cobicistat CL, Cmax, Tmax, Cmin and AUC0-24.
- Extension phase: Response rate (CR, CRi, CR/CRi, CRh, CR/CRh, CRMRD-, CR/CRiMRD-, CR/CRhMRD-, and MLFS).
- Event free survival (EFS).
- Relapse-free survival (RFS).
- Incidence and severity of adverse events according to CTCAE version 5.0.
- Early (30-day and 60-day) mortality (in general, non-leukemic).
- Time to next cycle, defined as the time from the start of the cycle until the start of the next cycle.
- OS of AZA/VEN/COBI treated patients in comparison with a real-world data cohort treated during the same time period and monitored by the Dutch Cancer registry.
- Prognostic/predictive impact of disease-associated genetic changes at diagnosis.
- Relapse-associated genetic changes (determined at relapse).
- Clonal evolution during treatment.
- Exposure-response and exposure-toxicity relation of venetoclax in patients with AML.
- Cost-savings on venetoclax drug costs.
- Adherence to venetoclax and cobicistat.
研究者
G. Huls
Scientific
Haemato Oncology Foundation For Adults Netherlands
研究点 (19)
Loading locations...
相似试验
招募中
2 期
A Multicenter, Open-Label, Dose-Finding Clinical Trial to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of RVU120 in Combination with Venetoclax in Participants with Acute Myeloid Leukemia Who Failed Prior Therapy with Venetoclax and a Hypomethylating Agent (RIVER-81)Acute Myeloid Leukemia2023-505911-19-00Ryvu Therapeutics S.A.129
尚未招募
2 期
PreVent-ACaLLChronic Lymphocytic Leukemia2024-511072-33-00Rigshospitalet50
招募中
2 期
BEACON: A randomised phase IIb trial of BEvACizumab added to Temozolomide ± IrinOtecan for children with refractory/relapsed NeuroblastomaNeuroblastoma2024-518931-12-00The University Of Birmingham122
招募中
不适用
Efficacy of Dose-Adjusted Regimen on Survival in Frail Adults With Acute Lymphoblastic LeukemiaLeukemiaNCT07258043Hospital General de Mexico45
进行中（未招募）
1/2 期
抗 PD-1 和 VEGF 双特异性抗体 AK112 联合治疗晚期肝细胞癌的 Ib/Ⅱ期临床研究CTR20243030280