An Open-label, Multicenter, Dose Escalation Phase 1b Study to Assess the Safety and Pharmacokinetics of Subcutaneous Delivery of Daratumumab with the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Subjects with Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma - plasma cell myeloma10018865
- Registration Number
- NL-OMON50498
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
- > /<= 18 years of age
- documented secretory multiple myeloma based on International Myeloma Working
Group (IMWG) criteria
-e vidence of relapsed or refractory disease on the most recent prior treatment
- at least 2 prior lines of therapy including a proteasome inhibitor (PI) and
an immunomodulatory drug (IMiD);
- an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0,
1, or 2
- Prior Daratumumab of other anti-CD38 therapies
-Prior Anti- myeloma treatment within 2 weeks before Cycle 1 Day 1
- Prior allogenic stem cell transplant
- Prior autologous stem cell transplantation (ASCT) within 12 weeks before
Cycle 1 Day 1
- Participant has a history of malignancy (other than multiple myeloma) within
5 years before Cycle 1 Day 1 (exceptions are squamous and basal cell carcinomas
of the skin and carcinoma in situ of the cervix, or malignancy that in the
opinion of the Investigator, with concurrence with the Sponsor's medical
monitor, is considered cured with minimal risk of recurrence)
Subject is:
* known to be seropositive for human immunodeficiency virus (HIV)
* seropositive for hepatitis B (defined by a positive test for hepatitis B
surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects 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) DNA levels. Those who are PCR positive will be
excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV
vaccination (Anti HBs positivity as the only serologic marker) AND a known
history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
* 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).
Subject has either of the following:
* Chronic obstructive pulmonary disease (COPD) with 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 is
<50% of predicted normal.
* Known moderate or severe persistent asthma within the past 2 years, or
uncontrolled asthma of any classification. Note that subjects who currently
have controlled intermittent asthma or controlled mild persistent asthma are
allowed to participate in the study.
* Subjects with a history of asthma and subjects with a history of COPD who
have a FEV1<80% at screening are excluded from the *3+3* portions of the
corticosteroid tapering cohorts in Part 3.
Clinically significant cardiac disease, including:
* myocardial infarction within 6 months before Cycle 1 Day 1, or an unstable or
uncontrolled disease/condition related to or affecting cardiac function (eg,
unstable angina, congestive heart failure, New York Heart Association Class
III-IV);
* uncontrolled cardiac arrhythmia (NCI-CTCAE [Version 4.03] Grade 2 or higher)
or clinically significant electrocardiogram (ECG) abnormalities; or
* screening 12-lead ECG showing a baseline QT interval as corrected (QTc) >470
msec.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PHARMACOKINETIC EVALUATIONS<br /><br>Blood samples will be obtained from all subjects to characterize the<br /><br>pharmacokinetics of daratumumab.<br /><br>The primary pharmacokinetic endpoint is the observed serum concentration of<br /><br>Daratumumab prior to the next drug administration at the end of weekly dosing<br /><br>(just prior to administration of Cycle 3 Day 1 dose).<br /><br><br /><br>SAFETY EVALUATIONS<br /><br>Safety evaluations will include adverse event monitoring, physical<br /><br>examinations, electrocardiograms (ECGs), photographs of SC infusion sites, SC<br /><br>infusion site evaluations, clinical laboratory parameters (hematology and<br /><br>chemistry), vital sign measurements, and ECOG performance status.</p><br>
- Secondary Outcome Measures
Name Time Method