M. Kahler
Conditions
Interventions
The administration of SGN-40 and bortezomib according to protocol
Sponsors
Genentech
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Documented pathologic diagnosis of multiple myeloma that has relapsed or failed to respond after treatment with at least one prior systemic therapy (other than corticosteroid monotherapy) • Measurable disease, defined as follows: Serum M-protein >= 1 g/dL (>= 10 g/L) Urine M-protein >= 200 mg/24 hr urine collection Involved FLC level >= 10 mg/dL (>= 100 mg/L, provided serum FLC ratio is abnormal) • At least one prior systemic therapy other than single-agent corticosteroids • European Union patients must have had prior bone marrow transplant (autologous) or be ineligible for transplant (note: the requirement for prior transplant is based on the approved indication for bortezomib in the European Union at the time the protocol was finalized). • If previously received bortezomib, demonstration of clinical response of any duration or stable disease with progression free interval of >= 6 months from the start of that therapy • If previously received bortezomib, must have recovered from bortezomib related toxicities and must have a peripheral neuropathy score of Grade = 12 weeks prior to Day 1 • Discontinuation of previous anticancer or investigational therapy for >= 21 days prior to treatment, or >= 90 days prior to treatment for previous monoclonal antibody administration • ECOG performance status of 0 or 1 (see Appendix F) • Life expectancy of > 3 months
Exclusion criteria
Exclusion criteria: • Prior treatment with a monoclonal antibody directed against CD40 • Prior allogeneic bone marrow transplant • Concurrent systemic corticosteroid therapy (except corticosteroid therapy 1.6 mg/dL AST or ALT greater than the upper limit of normal (ULN) Serum creatinine > 1.5 times upper limit of normal or calculated creatinine clearance = 3 years • Prior anaphylactic reaction to human immunoglobulin administration • Symptomatic hyperviscosity syndrome • Known intracranial disease or epidural disease Patients with lytic lesions of the cranium secondary to myeloma are eligible to enroll. • Active infection requiring parenteral antibiotics within 14 days of Day 1 • Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study • Serious, nonhealing wound, ulcer, or bone fracture • Clinically significant cardiac disease (New York Heart Association, Class III or IV), including preexisting arrhythmia, congestive heart failure, or cardiomyopathy • Any contraindication to bortezomib treatment, including hypersensitivity to bortezomib, boron, or mannitol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence and nature of DLT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Study Parameters / Outcome of the Study: • Occurrence, nature, and severity of treatment-emergent adverse events graded according to the NCI CTCAE v3.0 • Changes in vital signs, physical examination findings, ECOG performance score, and clinical laboratory results • Additional laboratory safety assessments, including serum immunoglobulin levels and immunogenicity assays (HAHA) Diagnostic Exploratory Endpoints • CD40 expression levels in bone marrow multiple myeloma cells pre-treatment • Gene expression analysis of bone marrow multiple myeloma cells pre-treatment • Frequency of polymorphisms in Fc*R DNA (optional) Pharmacodynamic Exploratory Endpoints • Changes in the characteristics of B- and T-cells, NK cells, monocytes, and other lymphocyte subsets • Changes in the levels of a panel of cytokines and chemokines assessed from peripheral blood Activity Endpoints • Objective response as determined by both the IMWG criteria and EBMT/IBMTR criteria • Event-free survival, defined as the time from Day 1 to the first occurrence of progression, relapse, death from any cause, or initiation of new multiple myeloma therapies • Duration of objective response, defined as the interval of time from the first occurrence of a documented objective response until progressive disease, start of another therapy for multiple myeloma, or death from any cause • Time to objective response, defined as the interval of time from Day 1 to the first occurrence of a documented objective response | — |
Countries
Netherlands
Outcome results
None listed