Clinical Trials

Inclusion Criteria:

• Provide written informed consent and be willing and able to comply with all study procedures.
• Adult, 18 years and older.
• AL amyloidosis Mayo stage IIIa 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:  
  • 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
  • At least one of the following:
    • Endomyocardial biopsy demonstrating AL cardiac amyloidosis; or
    • Echocardiogram demonstrating a mean left ventricular wall thickness > 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  
    • Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis.
• Planned first-line treatment for plasma cell disorder is CyBorD administered as Standard of Care (SoC).
• Adequate bone marrow reserve and hepatic and renal function as demonstrated by:
  • Absolute neutrophil count ≥ 1.0 x 10^9/L;
  • Platelet count ≥ 75 x 10^9/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);
  • Estimated glomerular filtration rate (eGFR) ≥ 15 mL/min.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use effective physician approved contraception from Screening to 90 days following the last study drug administration.
• Men must be surgically sterile or must agree to use effective physician approved contraception from Screening to 90 days following the last study drug administration.

Exclusion Criteria:

• Have any other form of amyloidosis other than AL amyloidosis.
• Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL amyloidosis and prior to randomization is allowed.  
• Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma or POEMS syndrome.
• 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.
• 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 cm^2) 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.
• Women who are breast feeding.