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

Not Recruiting

Trial ID: NCT03201965


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.

Official Title

A Randomized Phase 3 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 AL Amyloidosis

Stanford Investigator(s)

Michaela Liedtke
Michaela Liedtke

Associate Professor of Medicine (Hematology)


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

      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

   - 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

      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


drug: Cyclophosphamide

drug: Bortezomib

drug: Dexamethasone, 40 mg

drug: Daratumumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Mani Gupta

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