SHS_492352 BENW CBAY 16145

A Phase 1b/2 Trial to Evaluate the Safety and Efficacy of Radium-223 Dichloride (BAY88-8223) in Combination With Bortezomib and Dexamethasone in Early Relapsed Multiple Myeloma

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 approximately 30 total subjects in all dose cohorts combined will be treated in the phase 1b part of the study and approximately 196 subjects will be enrolled in the phase 2 part of the study.

Inclusion Criteria:

Documented monoclonal plasma cells as defined by their institutional standard in the bone marrow >=10% at some point in their disease history or presence of a biopsy proven plasmacytoma
Received at least 1 and not more than 3 previous lines of treatment and have had a response to treatment (i.e., achieved a minimal response [MR] or better) according to the International Myeloma Working Group (IMWG) uniform response criteria
Non-refractory to bortezomib or another proteasome inhibitor (PI), like ixazomib and carfilzomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy or another PI therapy, like ixazomib and carfilzomib)
Progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment
Measurable disease defined as at least 1 of various values listed in the protocol (according to central laboratory results)
≥1 bone lesion identifiable by radiograph, computed tomography, positron emission tomography - computed tomography (PET CT), or magnetic resonance imaging (MRI)
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
Adequate hepatic function, with bilirubin ≤1.5 x upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN
Absolute neutrophil count (ANC) ≥1.5 × 10e9/L, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or platelet concentrates and independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF)
International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN. PT can be used instead of INR if ≤ 1.5 x ULN

Exclusion Criteria:

Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 4 weeks prior to first dose, unless tapered and on a stable dose (prednisone ≤10 mg/day orally or equivalent) for at least 1 week
Known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light chain (AL) amyloidosis
Plasma cell leukemia
Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
Radiation therapy in the previous 4 weeks prior to first dose except if given for pain management and involves less than 10% of the bone marrow
Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical
Congestive heart failure
Neuropathy ≥ Grade 2 or Grade 1 with pain
Phase I/II
William Bensinger, M.D.
Neil Bailey
  • Swedish Medical Center