A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis

The purpose of this study is to evaluate the efficacy and safety of daratumumab plus cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD alone in treatment of newly diagnosed amyloid light chain (AL) amyloidosis participants.

Participant involved in study for approx. 8 years duration includes Screening Phase (complete clinical evaluation will be done), Treatment Phase (monitoring of adverse events (AEs), laboratory abnormalities and clinical response), Post-Treatment Observation Phase (disease evaluations will be done) and a Long-term Follow-up Phase (Subsequent anticancer treatment, response to subsequent treatment, date of progression and survival status will be obtained every 16 weeks).The primary hypothesis is that daratumumab in combination with CyBorD will improve the overall complete hematological response rate compared to CyBorD alone in AL amyloidosis participants. Safety will be assessed by AEs, laboratory test results, electrocardiogram, vital sign measurements, physical examination, and Eastern Cooperative Oncology Group (ECOG) performance status.

Eligibility Criteria:
Inclusion Criteria:

* Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance
* Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:

  1. serum monoclonal (M)-protein greater than or equal (\>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation \[IFE\] performed at a central laboratory)
  2. serum free light chain greater than or equal to (\>=) 50 milligram/Liter (mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) \>= 50 mg/L
* One or more organs impacted by AL amyloidosis according to consensus guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2

Exclusion Criteria:

* Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization
* Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, \>= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia
* Evidence of significant cardiovascular conditions as specified below:

  1. NT-ProBNP \> 8500 nanogram per liter (ng/L)
  2. New York Heart Association (NYHA) classification IIIB or IV heart failure
  3. Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram \[ECG\] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
  4. Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months
  5. For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
  6. Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators \[ICD\] is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study)
  7. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \> 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc interval
  8. Supine systolic blood pressure \< 90 millimeter of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of \> 20 mmHg despite medical management (eg, midodrine, fludrocortisones) in the absence of volume depletion
* Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted
* Known to be seropositive for human immunodeficiency virus (HIV)
* Any one of the following:

  1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
  2. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy)
* Grade 2 sensory or Grade 1 painful peripheral neuropathy