Inclusion Criteria:

• Each patient must meet the following criteria to be enrolled in this study.
  • Be able to and provide written informed consent and be willing and able to comply with all study procedures
  • Adult, 18 years and older
  • AL amyloidosis Mayo stage IIIb based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement at the time of Screening
  • Measurable hematologic disease at Screening as defined by at least one of the following:
    • Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or
    • Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or
    • Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL
  • Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid deposits by at least one of the following:
    • Immunohistochemistry or
    • Mass spectrometry or
  • Characteristic electron microscopy appearance
  • 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
  • Planned first-line treatment for plasma cell disorder is a CyBorD-based regimen administered as Standard of Care (SoC)
  • Adequate bone marrow reserve and hepatic function as demonstrated by:
    • Absolute neutrophil count ≥ 1.0 x 109/L
    • Platelet count ≥ 75 x 109/L
    • Hemoglobin ≥ 9 g/dL
    • Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless due to Gilbert's syndrome.
    • Aspartate aminotransferase (AST) ≤ 3 x ULN
    • Alanine aminotransferase (ALT) ≤ 3 x ULN
    • Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone)
  • 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
  • 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.

Exclusion Criteria:

• Patients who meet any of the following criteria will not be permitted entry to the study.
  • Have any other form of amyloidosis other than AL amyloidosis
  • Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after screening laboratory samples are obtained and prior to randomization is allowed.
  • Has POEMS syndrome or multiple myeloma defined as clonal bone marrow plasma cells > 10% or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of the following CRAB features:
    • a. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
    • i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1mg/dL) higher than the ULN or > 2.75 mmol/L (> 11mg/dL)
    • ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177mol/L (> 2mg/dL)
    • iii. Anemia: hemoglobin value of > 20g/L below the lowest limit of normal, or a hemoglobin value < 100g/L
    • iv. Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has < 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
  • OR
    • b. Any one of the following biomarkers of malignancy:
    • i. 60% or greater clonal plasma cells on bone marrow examination
    • ii. More than one focal lesion on MRI that is at least 5mm or greater in size
  • 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
  • Taking prednisone or its equivalent > 10 mg/day
  • Taking doxycycline
  • Receiving dialysis
  • Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted.
  • 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.
    • Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening
    • Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2) or severe congenital heart disease
    • 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.)
    • QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval.
  • There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
    • First degree Atrioventricular (AV)-block
    • Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)
    • Right or left bundle branch block
    • 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)
  • 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
  • There is active malignancy (including lymphoma) with the exception of any of the following:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
    • Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years
    • Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL
    • Other localized and/or low risk malignancies may be permitted with Medical Monitor approval.
  • Have received an investigational drug/device in another clinical investigational study within 60 days before Screening
  • Hypersensitivity to the study drug
  • Have received a live vaccine within 4 weeks prior to first dose of CyBorD
  • Women who are breast feeding
  • 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.