A study to evaluate the safety and efficacy of study drug radium-223 dichloride when given in combination with bortezomib and dexamethasone in patients with multiple myeloma that has recurred
- Conditions
- Relapsed multiple myelomaMedDRA version: 19.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002438-58-ES
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 226
Subjects must meet the following criteria for inclusion in the study (applicable to both parts of the study):
1. Males or females =18 years of age
2. Have provided written informed consent. Subjects must be able to understand and be willing to sign the written informed consent, expressing their willingness and ability tocomply with protocol-required treatment and assessment schedule, including follow-up visits. A signed ICF must be appropriately obtained prior to the conduct of any trial-specific procedure.
3. Subject must have 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
4. Subjects must have 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 IMWG uniform response criteria; see Definition of terms section for description of lines of therapy
5. Subject must be non-refractory to bortezomib or another 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)
6. Subjects must have had progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment
7. Subjects must have measurable disease defined as at least 1 of the following (according to central laboratory results):
- Serum M-protein defined by the following:
* IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL
* IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level =0.5 g/dL
- Urine M-protein =200 mg/24 hours (any immunoglobulin heavy chain type)
- Serum free light chain (FLC) =10 mg/dL with abnormal ratio
8. =1 bone lesion identifiable by radiograph, computed tomography, PET-CT, or MRI
9. Life expectancy of at least 3 months
10. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2
11. Adequate hepatic function, with bilirubin =1.5 x ULN, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0 x ULN
12. Absolute neutrophil count (ANC) =1.5 × 10E9/L, hemoglobin (Hb) =9.0 g/dL, and platelet count =75.0 × 109/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)
13. 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
14. Calculated or measured creatinine clearance of =30 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - age) x mass (kg)/(72 x creatinine mg/dL)]. Multiply result by 0.85 if female
15. Female subjects of child-bearing potential must have a negative serum pregnancy test within 72 hours before the first dose. Post-menopausal females (age =55 years and 1 year or more of amenorrhea; OR age <55 years and 1 year or more of amenorrhea with an estradiol assay <20 pg/mL; OR bilateral oophorectomy) and surgically sterilized females are exempt from a pregnancy test.
16. a) Female subjects of child-bearing potential who are sexually active must agree to utilize, during treatment with and for 6 months after the last dose of radium-223 dichloride/placebo/ bortezomib/dexamethasone, 2 reliable and accep
Subjects must not meet any of the exclusion criteria listed below (applicable to both parts of the study):
1. 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
2. Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light-chain (AL) amyloidosis
3. Plasma cell leukemia (defined by plasma cell >20%, and/or an absolute plasma cell count of >2 x 10E9/L in peripheral blood)
4. 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)
5. 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
6. Administration of an investigational therapeutic study drug within 4 weeks or within 5 drug half-lives (t1/2), whichever time is greater, prior to first dose
7. Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical
8. Major surgery within 4 weeks prior to first dose (central line placement is not considered a major surgery)
9. Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, cardiomyopathy, clinically relevant ventricular arrhythmia, pericardial disease, unstable angina or myocardial infarct in the previous 6 months prior to first dose, left ventricular ejection fraction <40%
10. Acute diffuse infiltrative pulmonary disease
11. Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
12. Known HIV infection or subjects who are known to be HIV seropositive
13. Subject with active hepatitis B or C infection at screening; subjects with known history of occult or hepatitis B virus (HBV) infection (defined as positive hepatitis B core antibody [HBcAb] and negative hepatitis B surface antigen [HBsAg]), but have undetectable HBV DNA at screening may be included. Subjects with history of positive for hepatitis C virus (HCV) antibody must be negative for HCV RNA by polymerase chain reaction (PCR) assessment or similar technology to be included.
14. Any history of malignancy within the past 3 years except adequately treated a) basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, c) prostate carcinoma in situ < Gleason Score 6 with stable PSA, or d) breast carcinoma in situ
15. Neuropathy = Grade 2 or Grade 1 with pain
16. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
17. Hypersensitivity to radium-223 dichloride, bortezomib, or dexamethasone or their excipients
18. Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
19. Female subjects who are pregnant or lactating
20. Serious psychiatric condition that could interfere with compliance of treatment
21. Close affiliation with the investigational site (e.g., a close relative of the Investigator, dependent person [e.g., employee or student of the investigational site])
22. P
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method