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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03201965




Registration number
NCT03201965
Ethics application status
Date submitted
27/06/2017
Date registered
28/06/2017
Date last updated
24/05/2024

Titles & IDs
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
Secondary ID [1] 0 0
2016-001737-27
Secondary ID [2] 0 0
CR108193
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyloidosis 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone, 40 mg
Treatment: Drugs - Daratumumab

Active Comparator: CyBorD alone (cyclophosphamide/bortezomib/dexamethasone) - Participants will receive dexamethasone (40 milligrams [mg] orally or intravenous [IV] dose), followed by cyclophosphamide (300 milligram per meter square [mg/m^2] orally or IV dose), then bortezomib (1.3 mg/m^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles.

Experimental: CyBorD plus Daratumumab - Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m^2 orally or IV dose weekly) and bortezomib (1.3 mg/m^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years.


Treatment: Drugs: Cyclophosphamide
Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose.

Treatment: Drugs: Bortezomib
Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection.

Treatment: Drugs: Dexamethasone, 40 mg
Participants of CyBorD alone arm will receive 40 mg dexamethasone orally or IV dose. Participants of CyBorD plus daratumumab arm will receive dexamethasone 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg.

Treatment: Drugs: Daratumumab
Participants will receive 1800 mg of daratumumab subcutaneously.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Overall Complete Hematologic Response (CHR)
Timepoint [1] 0 0
Up to 2.4 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
16/08/2024
Actual
Sample size
Target
Accrual to date
Final
416
Recruitment in Australia
Recruitment state(s)
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Box Hill Hospital - Box Hill
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Sir Charles Gairdner Hospital - Nedlands
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Westmead Hospital - Westmead
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Princess Alexandra Hospital - Woolloongabba
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3128 - Box Hill
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6009 - Nedlands
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2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03201965
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03201965