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Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02928029
Recruitment Status : Recruiting
First Posted : October 7, 2016
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Placebo Drug: Bortezomib Drug: Dexamethasone Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 226 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 10, 2017
Estimated Primary Completion Date : April 24, 2022
Estimated Study Completion Date : April 24, 2022


Arm Intervention/treatment
Experimental: Phase1, arm1: 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.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection
Drug: Bortezomib
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg
Experimental: Phase1, arm2: Radium-223 dichloride+SOC
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.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection
Drug: Bortezomib
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg
Experimental: Phase1, arm3: Radium-223 dichloride+SOC
Phase 1: Radium-223 dichloride; 88 kBq/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection
Drug: Bortezomib
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg
Placebo Comparator: Phase2, arm1: Placebo+SOC
Phase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone.
Drug: Placebo
Matching placebo
Drug: Bortezomib
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg
Experimental: Phase2, arm2: Radium-223 dichloride+SOC
Phase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection
Drug: Bortezomib
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg



Primary Outcome Measures :
  1. Joint positive adjudication of safety summary in Phase 1b by steering committee (Yes/No) [ Time Frame: At approximately 13 months ]
    The Steering Committee will include multiple myeloma experts and hemato oncologists and investigators.

  2. Progression-free survival (PFS) in Phase 2 [ Time Frame: Up to 50 months ]
    PFS defined as the time (in days) from date of randomization to disease progression


Secondary Outcome Measures :
  1. Objective response rate (ORR) in Phase 1b [ Time Frame: Approximately 12 months ]
    In the proportion of subjects in the analysis population who have complete response (CR), stringent complete response (sCR), very good partial response (VGPR), partial response (PR), or stable disease (SD)

  2. Duration of response in Phase 1b [ Time Frame: Approximately 12 months ]
    Defined as the time (in days) from the date of first response to treatment (CR, sCR, VGPR, PR) to the date of disease progression or death

  3. Number of participants with adverse events in phase 2 [ Time Frame: Up to 25 months ]
    AEs will be collected and recorded on an ongoing basis throughout the study

  4. Overall survival (OS) in Phase 2 [ Time Frame: Up to 25 months ]
    Defined as the time (in days) from date of randomization until death from any cause

  5. Time to Symptomatic Skeletal Event (SSE) in Phase 2 [ Time Frame: Up to 25 months ]
    Defined as the time (days) from the date of randomization to the date of the first on-study SSE

  6. Symptomatic skeletal event free survival in Phase 2 [ Time Frame: Up to 25 months ]
    Defined as the time from randomization to the occurrence of 1 of the following: First on-study SSE or Death from any cause if death occurs before a documented SSE

  7. Time to pain progression in Phase 2 [ Time Frame: Up to 25 months ]
    Defined as the occurrence of either a pain increase or an increase in pain management with respect to baseline, whichever occurs first

  8. Duration of response in Phase 2 [ Time Frame: Up to 25 months ]
    Defined as the time (in days) from the date of first response to treatment (CR, sCR, VGPR, PR) to the date of disease progression or death

  9. Objective Response Rate (ORR) in Phase 2 [ Time Frame: Up to 25 months ]
    In the proportion of subjects in the analysis population who have complete response (CR), stringent complete response (sCR), very good partial response (VGPR), partial response (PR), or stable disease (SD)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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 International Myeloma Working Group (IMWG) uniform response criteria
  • Subject must be 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)
  • Subjects must have had 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 (according to central laboratory results):

    • Serum M-protein ≥1 g/dL 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
  • ≥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
  • Subjects with 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 (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%
  • Neuropathy ≥ Grade 2 or Grade 1 with pain

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02928029


Contacts
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

Locations
United States, California
Pacific Oncology/Hematology Associates Recruiting
Encinitas, California, United States, 92024-1375
California Cancer Associates for Research & Excellence, Inc. Not yet recruiting
Fresno, California, United States, 93720
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109-4417
Korea, Republic of
National Cancer Center Recruiting
Goyang-si, Gyeonggido, Korea, Republic of, 410-769
Kyungpook National University Hospital Not yet recruiting
Daegu, Korea, Republic of, 700-701
Chonnam National University Hwasun Hospital Not yet recruiting
Jeollanam-do, Korea, Republic of, 519-763
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 135-710
Seoul St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of, 137-701
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 138-736
Spain
Institut Català d'Oncologia Badalona Not yet recruiting
Badalona, Barcelona, Spain, 08916
Hospital Universitari Son Espases Recruiting
Palma de Mallorca, Illes Baleares, Spain, 07120
Ciutat Sanitària i Universitaria de la Vall d'Hebron Not yet recruiting
Barcelona, Spain, 08035
Hospital Universitario de la Princesa Not yet recruiting
Madrid, Spain, 28006
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Hospital Universitario Dr. Peset Not yet recruiting
Valencia, Spain, 46017
Sponsors and Collaborators
Bayer

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02928029     History of Changes
Other Study ID Numbers: 18987
2016-002438-58 ( EudraCT Number )
First Posted: October 7, 2016    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Radium-223 dichloride
bortezomib
dexamethasone
early relapsed multiple myeloma
combination therapy multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Radium Ra 223 dichloride
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents