EUCTR2021-003008-42-GR进行中（未招募）1 期
A Single-Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.0 个研究点目标入组 159 人开始时间: 2021年12月6日最近更新:
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 159
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. At least 18 years of age (or the legal age of consent in the jurisdiction
- •in which the study is taking place, whichever is greater) at the time of
- •signing the informed consent.
- •2.Understands and voluntarily provides written informed consent as
- •described in Section 10.1.2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •3.A biopsy-confirmed diagnosis of AL amyloidosis based on one of the
- •following: histopathology (polarizing light microscopy demonstrating
- •green birefringent material in congo red-stained tissue specimens
- •confirmed by immunohistochemistry demonstrating light chain
- •deposition without the presence of transthyretin), the presence of
- •characteristic appearance on electron microscopy, or mass spectrometry
- •typing of amyloid.
- •4.Requires treatment for AL amyloidosis and has received at least one,
- •and no more than three, prior lines of therapy as follows:
- •Prior therapy can include HSCT or treatment with an alkylating agent,
- •proteasome inhibitor, immunomodulatory agent, or daratumumab;
- •If intolerance to a prior therapy resulted in failure to complete at least
- •one cycle (or for daily therapeutics, 4 weeks) of treatment because of
- •AEs, that will not be considered as a prior line of therapy.
- •5.Measurable disease defined by dFLC =20 mg/L.
- •6.History of organ involvement that included at least one of the following
- •(current measurable organ disease is not required for enrollment):
- •a. Renal: Albuminuria >0.5 g/day by 24-hour urine collection;
- •b. Cardiac: Mean left ventricular wall thickness on echocardiogram more
- •than 12 mm in the absence of a history of hypertension or valvular heart
- •disease, or unexplained low voltage (<0.5 mV) on ECG; or NT-ProBNP
- •>332 ng/L (or BNP >81 ng/L) in the absence of renal failure;
- •c. Hepatic: Hepatomegaly on PE or ultrasound or alkaline phosphatase
- •>1.5 x the upper limit of normal (ULN);
- •d. Gastrointestinal: Direct biopsy verification of amyloid deposition and
- •gastrointestinal symptoms such as gastrointestinal bleeding or diarrhea;
- •e. Neurologic: Symmetrical lower extremity sensorimotor peripheral
- •neuropathy or autonomic neuropathy including gastric motility disorder,
- •pseudo-obstruction, or voiding dysfunction unrelated to direct organ
- •infiltration.
- •7.Assessment of t(11;14) status by FISH on bone marrow aspirate.
- •8. At least 3 months from HSCT or the shorter of 30 days or 5 halflives from previous drug or biologic therapy or any investigational
- •treatment prior to Cycle 1 Day 1.
- •9.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
- •score of =2.
- •10.Adequate bone marrow function as follows:
- •a. Hemoglobin =8.0 mg/dL (0.08 g/L).
- •b.Absolute neutrophil count =1.5 x 109/L.
- •c.Platelet count =50 x 109/L.
- •11.Adequate organ function as follows:
- •a.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
- •b.Alkaline phosphatase =5 x ULN.
- •c.Total bilirubin =1.5 x ULN except in subjects with Gilbert syndrome.
- •d.Serum albumin = 2 g/dL (20 g/L).
- •e.Estimated glomerular filtration rate (eGFR) =45 mL/min/1.73 m2 in Part
- 另有 6 项未显示
排除标准
- •1. Presence of non-AL amyloidosis, including wild type or mutated transthyretin
- •amyloidosis (ATTR).
- •2. Diagnosis of multiple myeloma according to the 2014 International
- •Myeloma Working Group diagnostic criteria (Rajkumar 2014).
- •3. Mayo2012 Stage IV disease, defined as follows:
- •a. NT-ProBNP = 1800 ng/L.
- •b. cTnT = 0.025 ng/mL (0.025 µg/L).
- •c. dFLC = 180 mg/L (18 mg/dL).
- •4. Any of the following cardiac conditions:
- •a. New York Heart Association (NYHA) Class III or IV heart failure at
- •Screening (Table 7).
- •b. History of sustained ventricular tachycardia or fibrillation, or
- •ventricular arrhythmias (ventricular tachycardia sustained for over 30
- •seconds, 1 or more occurrences of non-sustained ventricular tachycardia
- •of 3 or more consecutive ventricular beats or more than 20 ventricular
- •pairs per 24 hours) on 24-hour ambulatory ECG monitoring, unless the
- •subject has an implantable cardioverter defibrillator.
- •c. Corrected QT interval (QTc) > 500 msec (using Fridericia's correction;
- •Section 8.5.4) on a 12-lead ECG.
- •d. Atrial fibrillation with inadequate anti-coagulation (if indicated).
- •e. Second- or third-degree atrioventricular block (Mobitz type I is
- •permitted).
- •f. History of myocardial infarction, coronary stent placement, or coronary
- •artery bypass grafting within 6 months of enrollment.
- •g. Left ventricular ejection fraction (LVEF) by echocardiogram < 35%.
- •h. Supine systolic blood pressure < 90 mm Hg or symptomatic
- •orthostatic hypotension (decrease in systolic blood pressure upon
- •standing of > 20 mm Hg in the absence of hypovolemia and despite
- •medical management).
- •5. Positive serum antibody tests for hepatitis B surface antigen or
- •hepatitis C (subjects previously treated for hepatitis B or C who test
- •positive can be enrolled if negative for active infection according to
- •applicable viral load and/or antigen testing).
- •6. Women who are pregnant or intending to become pregnant or who are
- •breastfeeding or intending to breastfeed, during the study.
- •7. Concurrent treatment with drugs or consumption of foods that are
- •strong cytochrome P450 enzyme (CYP) 3A4 inhibitors or strong or
- •moderate CYP3A4 inducers; such treatments should be discontinued 5
- •half-lives, or for CYP3A4 inducers 14 days, prior to the first dose of ZNd5.
- •8. Prior treatment with ZN-d5, venetoclax, navitoclax, obatoclax or any
- •other small-molecule BCL-2 inhibitor, or known hypersensitivity to ZN-d5
- •or any of its inactive ingredients.
- •9. Any concurrent medical condition that would make a potential
- •subject a poor candidate for this study, including (but not limited to) uncontrolled serious infection, active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, uncontrolled
- •pulmonary disease, severe diarrhea (=Grade 3), cirrhosis, any
- •condition likely to require the use of systemic corticosteroids for more
- •than 1 week during the course of this study, or major surgery within 28
- •days of enrollment.
- •10. Any psychiatric illnesses or social situation that would preclude
- •understanding the informed consent, maintaining study compliance, or
- 另有 5 项未显示
研究者
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