A Randomized Phase 3 Study to Evaluate the Efficacy and Safety of Daratumumab in Combination with Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared With CyBorD Alone in Newly Diagnosed Systemic AL Amyloidosis
- Conditions
- Amyloid Light Chain Amyloidosis/clonal neoplasm of the plasma cell10035227
- Registration Number
- NL-OMON48611
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
# 18 years of age or older.
# Histopathological diagnosis of amyloidosis based on detection by
IHC 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, if required
# Measurable disease of amyloid light chain amyloidosis as defined by at least
ONE of
the following:
* serum M- protein >=0.5 g/dL by protein electrophoresis (routine serum protein
electrophoresis and immunofixation (IFE) performed at a central laboratory),
* serum free light chain >=5.0 mg/dL with an abnormal kappa:lambda ratio or the
difference between involved and uninvolved free light chains (dFLC) >=5mg/ dL.
# One or more organs impacted by AL amyloidosis according to consensus
guidelines
# Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
# Laboratory values as defined by the protocol
# 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% plasma cells in the bone
marrow, or hypercalcemia
# Evidence of significant cardiovascular conditions as specified below:
a. NT-ProBNP >8500 ng/L
b. New York Heart Association (NYHA) classification IIIB or IV heart failure
c. 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 ECG changes) or uncorrected valvular disease
and not primarily due to AL amyloid cardiomyopathy
d. 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
e. For subjects with congestive heart failure, cardiovascular-related
hospitalizations within 4 weeks prior to randomization
f. Subjects 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/ICD is indicated but
not placed (Subjects who do have a pacemaker/ICD are allowed on study)
g. Screening 12-lead ECG showing a baseline QT interval as corrected by
Fridericia*s formula (QTcF) >500 msec. Subjects who have a pacemaker may be
included regardless of calculated QTc interval.
h. Supine systolic blood pressure <90 mm Hg, 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
# Any form of non-AL amyloidosis, including wild type or mutated (ATTR)
amyloidosis.
# History of malignancy (other than AL amyloidosis) within 3 years before the
date of
randomization (see exceptions in the protocol).
# Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume
in
1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for
subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of
predicted normal
# Moderate or severe persistent asthma within the past 2 years, or
currently has uncontrolled asthma of any classification.
# Known to be seropositive for HIV, known to be seropositive for Hep B or known
to be seropositive for Hep C
# Grade 2 sensory or Grade 1 painful peripheral neuropathy
#Subjects who are taking CYP3A4 inducers must discontinue their use at least 5
half-lives prior to the first dose of study treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is overall complete hematologic response rate.</p><br>
- Secondary Outcome Measures
Name Time Method