This study will be conducted in 2 parts. The phase 1b part will be an international, phase 1b, open-label, dose-escalation assessment of radium-223 dichloride administered with bortezomib and dexamethasone in subjects with relapsed multiple myeloma. The primary endpoint is to determine the optimal dose of radium-223 dichloride in combination with bortezomib/dexamethasone for the Phase 2 portion of the study. The phase 2 part will be an international, phase 2, double-blind, randomized, placebo-controlled assessment of radium-223 dichloride versus placebo administered with bortezomib and dexamethasone, in subjects with relapsed multiple myeloma. Up to 12 subjects in all dose cohorts combined will be treated in the phase 1b part of the study. Up to approximately 100 subjects will be enrolled in the phase 2 part of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
7
Sequential dose escalation in Intravenous (IV) injection
Matching placebo
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Dexamethasone is administered orally at 40 mg
Pacific Oncology/Hematology Associates
Encinitas, California, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
National Cancer Center
Goyang-si, Gyeonggido, South Korea
Seoul National University Hospital
Seoul, South Korea
Hospital Universitari Son Espases
Palma de Mallorca, Illes Baleares, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
Phase 1: MTD/RP2D Determined by the Incidence of DLTs
Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for the severity grade
Time frame: From the start of study medication through 3 weeks after administration of the second dose of radium-223 dichloride, assessed up to 9 weeks
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Drug-related TEAEs, and Treatment-emergent Serious AE
A treatment-emergent adverse event (TEAE) is defined as any event arising or worsening after start of study drug administration until the end of the treatment period
Time frame: From the start of study drug (radium-223 dichloride) to 30 days after last dose of study treatment (radium-223 dichloride, BOR, or DEX, whichever is last), assessed up to approximately 2 years
Phase 1: The Number of Subjects With Complete Response (CR) and Very Good Partial Response (VGPR)
Determined by International Myeloma Working Group (IMWG) uniform response criteria. CR: Negative immunofixation of serum and urine, disappearance of any soft-tissue plasmacytomas, and \<5% plasma cells in bone marrow; in patients for whom only measurable disease is by serum free light chain (FLC) level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required; 2 consecutive assessments are needed. VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component \<100 mg/24 hours (hrs); in patients for whom only measurable disease is by serum FLC level, \>90% decrease in difference between involved and uninvolved FLC levels, in addition to VGPR criteria, is required; 2 consecutive assessments are needed
Time frame: Up to approximately 2 years
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