Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Radium-223 dichloride, Bortezomib, Dexamethasone, Relapsed multiple myeloma, Combination therapy multiple myeloma
Eligibility Criteria
Inclusion Criteria:
- Subject must have documented monoclonal plasma cells in the bone marrow of ≥10%, as defined by their institutional standard at some point in their disease history or the presence of a biopsy proven plasmacytoma.
- Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to at least 1 prior Treatment in the past (i.e., achieved a minimal response [MR] or better) according to the IMWG uniform response criteria.
- Subject must be non-refractory to bortezomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
- Subjects must have documented evidence of progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment.
Subjects must have measurable disease defined as at least 1 of the following:
Serum M-protein defined by the following:
- IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL (measured by protein electrophoresis [PEP]);
- IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ≥0.5 g/dL (measured by PEP).
- Urine M-protein ≥200 mg/24 hours (any immunoglobulin heavy chain type measured by PEP).
- Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio in subjects with unmeasurable disease by serum or urine PEP.
- ≥1 bone lesion identifiable by radiograph, computed tomography (CT), positron emission tomography - computed tomography (PET-CT), or magnetic resonance imaging (MRI).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
- Adequate hepatic function, with total bilirubin ≤1.5 x upper limit of normal (ULN) (except for Gilbert Syndrome: total bilirubin < 3.0 x 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. Prothrombin time (PT) may 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.
- Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light-chain (AL) amyloidosis.
- Plasma cell leukemia (defined by plasma cell >20%, and/or an absolute plasma cell count of >2 x 10e9/L in peripheral blood).
- Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic (PK) half-lives (t1/2) of the treatment, whichever is longer, before the date of start of treatment.
- Radiation therapy in the previous 4 weeks prior to first dose.
- Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical.
- Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, unstable angina or myocardial infarction in the previous 6 months prior to first dose, or with a known left ventricular ejection fraction (LVEF) <40%, cardiomyopathy, pericardial disease, clinically relevant cardiac arrhythmia (CTCAE version 4.03 Grade 2 or higher), clinically significant ECG abnormalities, or screening 12-lead ECG showing a baseline prolonged QT interval (baseline QT interval as corrected by Fridericia's formula > 470 msec).
- Neuropathy ≥ Grade 2.
Sites / Locations
- Pacific Oncology/Hematology Associates
- Wake Forest Baptist Health
- Fred Hutchinson Cancer Research Center
- National Cancer Center
- Seoul National University Hospital
- Hospital Universitari Son Espases
- Hospital Universitario Virgen del Rocío
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Placebo Comparator
Experimental
Phase1, arm1: 33 kBq/kg Radium-223 dichloride+SOC
Phase1, arm2: 55 kBq/kg Radium-223 dichloride+SOC
Phase2, arm1: Placebo+SOC
Phase2, arm2: Radium-223 dichloride+SOC
Phase 1: Radium-223 dichloride; 33 kiloBecquerel (kBq)/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses plus SOC (standard of care) bortezomib/ dexamethasone.
Phase 1: Radium-223 dichloride; 55 kBq/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/ dexamethasone.
Phase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone.
Phase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone