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Phase 3 N=416 Randomized Treatment

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

Amyloidosis

Enrolled (actual)
416
Serious AEs
41.8%
Results posted
Mar 2021
Primary outcome: Primary: Percentage of Participants With Overall Complete Hematologic Response (CHR) — 18.1; 53.3 percentage of participants — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Cyclophosphamide (Drug); Bortezomib (Drug); Dexamethasone, 40 mg (Drug); Daratumumab (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Janssen Research & Development, LLC
Primary completion
Feb 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Overall Complete Hematologic Response (CHR)
18.1; 53.3 <0.0001 sig
SECONDARY
Major Organ Deterioration Progression-Free Survival (MOD-PFS)
30.23; NA
SECONDARY
Overall Survival (OS)
NA; NA
SECONDARY
Organ Response Rate (OrRR) at 6 Months: Cardiac Response
22.2; 41.5
SECONDARY
Organ Response Rate (OrRR) at 6 Months: Renal Response
27.4; 53.8
SECONDARY
Organ Response Rate (OrRR) at 6 Months: Liver Response
7.1; 40.0
SECONDARY
Percentage of Participants Who Achieved Complete Hematologic Response (CHR) at 6 Months
14.0; 50.3
SECONDARY
Time to Complete Hematologic Response (CHR)
85.00; 67.50
SECONDARY
Time to Cardiac Response
4.67; 3.84
SECONDARY
Time to Liver Response
10.61; 4.68
SECONDARY
Time to Renal Response
3.75; 1.91
SECONDARY
Time to Subsequent Non-cross Resistant Anti-plasma Cell Therapy
11.30; NA
SECONDARY
Duration of Complete Hematologic Response (CHR)
NA; NA
SECONDARY
Hematologic Very Good Partial Response (VGPR) or Better Rate
50.3; 79.0
SECONDARY
Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue
3.79; 2.07; 4.04; 3.93; 6.35; 2.77
SECONDARY
Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS)
-0.43; -0.19; -1.09; -1.42; -1.86; -0.17
SECONDARY
Change From Baseline in EORTC QLQ-C30 Global Health Status Score
-3.02; -2.72; -4.15; -3.83; -6.00; -1.70

Summary

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.

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:
  • 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)
  • 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:
  • NT-ProBNP > 8500 nanogram per liter (ng/L)
  • New York Heart Association (NYHA) classification IIIB or IV heart failure
  • 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
  • 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
  • For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
  • 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)
  • 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
  • Supine systolic blood pressure 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:
  • 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
  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03201965). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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