•每个病人必须符合以下标准参加本研究。1。能,并提供书面的知情同意,愿意和能够符合所有研究过程2。成年人,18岁及以上3。AL淀粉样变梅奥阶段希望基于2013年欧洲修改2004标准的梅奥诊所分期晚期患者的心脏介入时筛选4。定义的可测血液疾病筛查至少以下之一:1。参与/冷漠自由轻链的区别(dFLC) > 4 mg / dL或2。涉及自由轻链(iFLC) > 4 mg / dL异常比率或3。血清蛋白电泳(SPEP) m-spike > 0.5 g / dL 5。组织病理学诊断淀粉样变和确认的派生的淀粉样蛋白沉积至少以下之一:1。 Immunohistochemistry or 2. Mass spectrometry or 3. Characteristic electron microscopy appearance 6. Cardiac involvement as defined by: a. Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND b. At least one of the following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening or iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis 7. Planned first-line treatment for plasma cell disorder is a CyBorD-based regimen administered as Standard of Care (SoC) 8. Adequate bone marrow reserve and hepatic function as demonstrated by: 1. Absolute neutrophil count ≥ 1.0 x 109/L 2. Platelet count ≥ 75 x 109/L 3. Hemoglobin ≥ 9 g/dL 4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless due to Gilbert's syndrome. 5. Aspartate aminotransferase (AST) ≤ 3 x ULN 6. Alanine aminotransferase (ALT) ≤ 3 x ULN 7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone) 9. Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician approved contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer 10. Men must be surgically sterile or must agree to use effective physician approved contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of his PCD therapy, whichever is longer.
排除标准:
•满足下列标准的患者将不允许进入研究。1。有任何其他形式的半岛以外的淀粉样变性淀粉样变2。收到之前治疗淀粉样变或多发性骨髓瘤。最大曝光CyBorD-based纤毛运动治疗后2周的筛查实验室获得样本和随机化之前是被允许的。3所示。诗综合症或多发性骨髓瘤骨髓浆细胞> 10%定义为克隆或biopsy-proven骨骨髓浆细胞瘤和任何一个或多个下列蟹特点:a。最终器官损伤的证据,可以归因于底层浆细胞增生性疾病,特别是:i。血钙过多:血清钙> 0.25更易/ L (> 1 mg / dL)高于ULN或> 2.75更易/ L (> 11 mg / dL)。肾功能不全:肌酐清除率< 40毫升每分钟或血清肌酐> 177 mol / L (> 2 mg / dL) iii。贫血:血红蛋白值> 20 g / L低于正常的最低限制,或血红蛋白值< 100 g / L iv。骨骼病变:一个或多个溶骨的损伤骨骼放射显影术,CT,或PET / CT。克隆浆细胞如果骨髓< 10%,超过一个骨骼病变需要区分单独以最小的骨髓浆细胞瘤参与或b。下面任何一种恶性肿瘤的生物标记:i。60%或更大的克隆浆细胞在骨髓检查。 More than one focal lesion on MRI that is at least 5mm or greater in size 4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion 5. Taking prednisone or its equivalent > 10 mg/day 6. Taking doxycycline 7. Receiving dialysis 8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted. 9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor. 10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening 11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2) or severe congenital heart disease 12. Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Participants who do have a pacemaker or ICD are allowed in the study.) 13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval. 14. There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following: 1. First degree Atrioventricular (AV)-block 2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type) 3. Right or left bundle branch block 4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled ventricular rate [i.e., > 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed) 15. Have had major surgery within 4 weeks of randomization or is planning major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate 16. There is active malignancy (including lymphoma) with the exception of any of the following: 1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer 2. Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years 3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL 4. Other localized and/or low risk malignancies may be permitted with Medical Monitor approval. 17. Have received an investigational drug/device in another clinical investigational study within 60 days before Screening 18. Hypersensitivity to the study drug 19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD 20. Women who are breast feeding 21. Have any other medical, social or psychological factors that could affect the patient's safety or ability to consent personally or comply with study procedures.
•每个病人必须符合以下标准参加本研究。1。能,并提供书面的知情同意,愿意和能够符合所有研究过程2。成年人,18岁及以上3。AL淀粉样变梅奥阶段iii a 2004标准的基于2013年欧洲修改梅奥诊所分期晚期患者的心脏介入时筛选4。定义的可测血液疾病筛查至少以下之一:1。参与/冷漠自由轻链的区别(dFLC) > 4 mg / dL或2。涉及自由轻链(iFLC) > 4 mg / dL异常比率或3。血清蛋白电泳(SPEP) m-spike > 0.5 g / dL 5。组织病理学诊断淀粉样变和确认的派生的淀粉样蛋白沉积至少以下之一:1。 Immunohistochemistry or 2. Mass spectrometry or 3. Characteristic electron microscopy appearance 6. Cardiac involvement as defined by: a. Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND b. At least one of the following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening or iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis 7. Planned first-line treatment for plasma cell dyscrasia is a CyBorD-based regimen administered as Standard of Care (SoC) 8. Adequate bone marrow reserve and hepatic function as demonstrated by: 1. Absolute neutrophil count ≥ 1.0 x 109/L 2. Platelet count ≥ 75 x 109/L 3. Hemoglobin ≥ 9 g/dL 4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless due to Gilbert's syndrome. 5. Aspartate aminotransferase (AST) ≤ 3 x ULN 6. Alanine aminotransferase (ALT) ≤ 3 x ULN 7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone) 9. Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician approved contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer 10. Men must be surgically sterile or must agree to use effective physician approved contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of his PCD therapy, whichever is longer
排除标准:
•满足下列标准的患者将不允许进入研究。1。有任何其他形式的半岛以外的淀粉样变性淀粉样变2。收到之前治疗淀粉样变或多发性骨髓瘤。最大曝光CyBorD-based纤毛运动治疗后2周的筛查实验室获得样本和随机化之前是被允许的。3所示。诗综合症或多发性骨髓瘤骨髓浆细胞> 10%定义为克隆或biopsy-proven骨骨髓浆细胞瘤和任何一个或多个下列蟹特点:a。最终器官损伤的证据,可以归因于底层浆细胞增生性疾病,特别是:i。血钙过多:血清钙> 0.25更易/ L (> 1 mg / dL)高于ULN或> 2.75更易/ L (> 11 mg / dL)。肾功能不全:肌酐清除率< 40毫升每分钟或血清肌酐> 177 mol / L (> 2 mg / dL) iii。贫血:血红蛋白值> 20 g / L低于正常的最低限制,或血红蛋白值< 100 g / L iv。骨骼病变:一个或多个溶骨的损伤骨骼放射显影术,CT,或PET / CT。克隆浆细胞如果骨髓< 10%,超过一个骨骼病变需要区分单独以最小的骨髓浆细胞瘤参与或b。下面任何一种恶性肿瘤的生物标记:i。60%或更大的克隆浆细胞在骨髓检查。 More than one focal lesion on MRI that is at least 5mm or greater in size 4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion 5. Taking prednisone or its equivalent > 10 mg/day 6. Taking doxycycline 7. Receiving dialysis 8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted. 9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor. 10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening 11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2) or severe congenital heart disease 12. Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Participants who do have a pacemaker or ICD are allowed in the study.) 13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval. 14. There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following: 1. First degree Atrioventricular (AV)-block 2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type) 3. Right or left bundle branch block 4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled ventricular rate [i.e., > 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed) 15. Have had major surgery within 4 weeks of randomization or is planning major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate 16. There is active malignancy (including lymphoma) with the exception of any of the following: 1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer 2. Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years 3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL 4. Other localized and/or low risk malignancies may be permitted with Medical Monitor approval. 17. Have received an investigational drug/device in another clinical investigational study within 60 days before Screening 18. Hypersensitivity to the study drug 19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD 20. Women who are breast feeding 21. Have any other medical, social or psychological factors that could affect the patient's safety or ability to consent personally or comply with study procedures.