To establish the safety profile of daratumumab when given in combination with bortezomib and dexamethasone in subjects with relapsed or refractory MM
ID
Source
Brief title
Condition
- Plasma cell neoplasms
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary variable for this trial will be the incidence of AEs
Secondary outcome
Secondary variables are:
* The rate of response according to the International Uniform Response
Criteria21
* PK variables (AUC, Cmax, minimum or trough concentration in plasma [Cmin],
time to Cmax [Tmax], apparent clearance [CL], volume of distribution [V], and
t1/2)
* Time to progression
* Duration of response
* Progression-free survival
Background summary
Multiple myeloma (MM) is a plasma cell disorder, characterized by uncontrolled,
malignant proliferation and accumulation of plasma cells. In the majority of
patients, the malignant plasma cells produce a monoclonal protein (M protein or
paraprotein).
Multiple myeloma accounts for approximately 1% of all malignancies and 10% of
all hematologic malignancies, with a higher frequency in African Americans
where it accounts for 20% of all hematologic malignancies. At present, there is
no cure available.
Treatments include combination chemotherapy, proteasome inhibition,
immunomodulatory drugs, high-dose chemotherapy, and autologous stem cell
transplantation (auto SCT).
Study objective
To establish the safety profile of daratumumab when given in combination with
bortezomib and dexamethasone in subjects with relapsed or refractory MM
Study design
In this Phase I/II safety trial of daratumumab in combination with bortezomib
and low-dose dexamethasone, a standard Phase I 3 + 3 design is appropriate to
adequately observe DLTs associated with the regimen while not exposing an undue
number of subjects to doses that may be subtherapeutic. The dose escalation
part of the trial (Part 1) will be followed by a cohort expansion part (Part 2)
in which subjects will be enrolled at the MTD (or maximum tested dose)
determined during Part 1. Part 2 of this trial will allow for a greater degree
of experience with the combination therapy at what is expected to be a
therapeutic dose of daratumumab
Intervention
Skeletal Survey
A whole-body X ray or CT scan, including the cranium, is required. Additional
surveys (X ray, CT scan, or magnetic resonance imaging scan) may be performed
at the investigator*s discretion (eg, to confirm response, to evaluate new
symptoms or bone pain).
Blood and Urine sapmples will be taken for testing: Biochemistry, hematology,
HIV, Hepatitis B and Cytomegalovirus Serology, Pregnancy,Bone Marrow
Assessments ,Serum Immunoglobulin A, M, and G (M component), Urinalysis for M
component ,Serum Free Light Chain Ratio Prognostic Factors:
Pharmacokinetic/Pharmacodynamic Assessments of Daratumumab Concentration in
Serum
Study burden and risks
Skeletal Survey
A whole-body X ray or CT scan, including the cranium, is required. Additional
surveys (X ray, CT scan, or magnetic resonance imaging scan) may be performed
at the investigator*s discretion (eg, to confirm response, to evaluate new
symptoms or bone pain).
Blood and Urine sapmples will be taken for testing: Biochemistry, hematology,
HIV, Hepatitis B and Cytomegalovirus Serology, Pregnancy,Bone Marrow
Assessments ,Serum Immunoglobulin A, M, and G (M component), Urinalysis for M
component ,Serum Free Light Chain Ratio Prognostic Factors:
Pharmacokinetic/Pharmacodynamic Assessments of Daratumumab Concentration in
Serum
Bredgade 34
1253 Kopenhagen K
DK
Bredgade 34
1253 Kopenhagen K
DK
Listed location countries
Age
Inclusion criteria
- (Part 1) Have relapsed MM after receiving a minimum of 2 and a;maximum of 4 prior lines of therapy and be eligible for treatment with Bor/Dex. Subjects must be naive to Bortezomib treatment;- (Part 2) Have relapsed MM after receiving a minimum of 1 and a;maximum of 3 prior lines of therapy, but not have MM that is refractory to the last treatment, and be eligible for treatment with Bor/Dex. ;- Have measurable levels of M-component, defined as serum Mcomponent 1.0 g/dL and/or urine M-component 200 mg/24-hour;sample.;- Be older than or be 18 years of age.;- ECOG performance status (0-2).;- Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out.
Exclusion criteria
- Have previously received an allogenic stem cell transplant.;- Have received auto SCT within 12 weeks before the first infusion.;- Have received chemotherapy or any experimental drug or therapy;within 3 weeks before the first infusion.;- Have received bortezomib, lenalidomide, or thalidomide within 2 weeks before the first infusion.;- Have MM that is refractory to bortezomib, defined as not having a minimum clinical response of MR for at least 2 months during the last treatment with bortezomib).;- Must not be known to be seropositive for HIV
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005692-16-NL |
| CCMO | NL39334.041.12 |