EUCTR2021-003008-42-CY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, Inc0 个研究点目标入组 135 人开始时间: 2023年1月23日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 135
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 10.1.1, which includes compliance with the requirements and restrictions listed in the informed consent form (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 sample.
- •8.Adequate time since prior therapy before initiation of treatment with
- •ZN d5 (at least 3 months from HSCT or the shorter of 60 days or 5 halflives
- •from previous drug or biologic therapy or any investigational
- •treatment).
- •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 (80 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 for subjects with Gilbert syndrome.
- •d.Serum albumin = 2 g/dL (20 g/L).
- •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 ATTR
- •amyloidosis.
- •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
- •(Table 9).
- •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. Concurrent treatment with agents used to treat plasma cell disorders
- •or AL amyloidosis, including experimental agents; such treatments
- •should be discontinued the shorter of 60 days or 5 half-lives prior to the
- •first dose of ZN-d5.
- •9. 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.
- •10. 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
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研究者
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