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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT03201965
Date of registration: 27/06/2017
Prospective Registration: Yes
Primary sponsor: Janssen Research & Development, LLC
Public title: 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
Scientific 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
Date of first enrolment: October 5, 2017
Target sample size: 416
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/show/NCT03201965
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 3
Countries of recruitment
Australia Belgium Brazil Canada China Denmark France Germany
Greece Hungary Israel Italy Japan Korea, Republic of Mexico Netherlands
Poland Romania Spain Sweden Turkey United Kingdom United States
Contacts
Name:     Janssen Research & Development, LLC Clinical Trial
Address: 
Telephone:
Email:
Affiliation:  Janssen Research & Development, LLC
Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Amyloidosis
Intervention(s)
Drug: Bortezomib
Drug: Cyclophosphamide
Drug: Daratumumab
Drug: Dexamethasone, 40 mg
Primary Outcome(s)
Percentage of Participants With Overall Complete Hematologic Response [Time Frame: Approximately 3 years]
Secondary Outcome(s)
Change From Baseline in the 36-Item Short Form Survey version 2 (SF-36v2) Mental Component Summary (MCS) [Time Frame: Baseline, up to end of study (approximately 5 years)]
Change From Baseline in the EORTC QLQ-C30 Global Health Status Scale Score [Time Frame: Baseline, up to end of study (approximately 5 years)]
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Fatigue Scale Score [Time Frame: Baseline, up to end of study (approximately 5 years)]
Complete Hematologic Response (CHR) [Time Frame: Up to 2 years]
Duration of Complete Hematologic Response [Time Frame: Approximately 5 years]
Duration of Hematologic Very Good Partial Response (VGPR) or Better Response [Time Frame: Approximately 5 years]
Duration of Organ Response [Time Frame: Approximately 5 years]
Hematologic Very Good Partial Response or Better Rate [Time Frame: Approximately 3 years]
Major Organ Deterioration Progression-Free Survival (MOD-PFS) [Time Frame: Approximately 5 years]
Organ Response Rate (OrRR) [Time Frame: Approximately 5 years]
Overall Survival (OS) [Time Frame: Approximately 8 years]
Time to Cardiac Progression [Time Frame: Approximately 5 years]
Time to Cardiac Response [Time Frame: Approximately 5 years]
Time to Complete Hematologic Response [Time Frame: Approximately 3 years]
Time to Hematologic Very Good Partial Response (VGPR) or Better Response [Time Frame: Approximately 3 years]
Time to Liver Progression [Time Frame: Approximately 5 years]
Time to Liver Response [Time Frame: Approximately 5 years]
Time to Next Treatment (TNT) [Time Frame: Approximately 5 years]
Time to Renal Progression [Time Frame: Approximately 5 years]
Time to Renal response [Time Frame: Approximately 5 years]
Secondary ID(s)
2016-001737-27
54767414AMY3001
CR108193
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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