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Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02605356
Recruitment Status : Withdrawn (Study restarted under new study number 18987)
First Posted : November 16, 2015
Last Update Posted : October 7, 2016
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 of the phase 1b part 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. Randomization (1:1) in the phase 2 part will be stratified by:

  • Prior bortezomib treatment (yes, no)
  • Prior treatment (1 prior line of treatment, >1 prior line of treatment) Approximately 30 subjects (10 subjects per cohort) will be enrolled 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 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
Study Start Date : October 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: Radium-223 dichloride [Phase 1, dose 1]
Phase 1: Radium-223 dichloride; 30 kiloBecquerel (kBq)/kg body weight (33 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Bortezomib
Drug: Dexamethasone
Experimental: Radium-223 dichloride [Phase 1, dose 2]
Phase 1: Radium-223 dichloride; 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Bortezomib
Drug: Dexamethasone
Experimental: Radium-223 dichloride [Phase 1, dose 3]
Phase 1: Radium-223 dichloride; 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Bortezomib
Drug: Dexamethasone
Placebo Comparator: Placebo +SoC [Phase 2]
Phase 2: Matching placebo (isotonic saline) every 4 weeks for a total of 6 doses plus SoC (Standard of care) bortezomib/dexamethasone.
Drug: Placebo
Drug: Bortezomib
Drug: Dexamethasone
Experimental: Radium-223 dichloride + SoC [Phase 2]
Phase 2: Phase 1b-selected dose of radium-223 dichloride every 4 weeks for 6 doses plus SOC bortezomib/dexamethasone
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Bortezomib
Drug: Dexamethasone



Primary Outcome Measures :
  1. Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No) [ Time Frame: At 13 months ]
  2. Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression [ Time Frame: Up to 25 months ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) in Phase 1b, 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) [ Time Frame: Approximately 12 months ]
  2. Duration of response in Phase 1b, 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 [ Time Frame: Approximately 12 months ]
  3. Number of participants with adverse events in phase 2 [ Time Frame: Up to 25 months ]
  4. Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause [ Time Frame: Up to 25 months ]
  5. Time to Symptomatic Skeletal Event (SSE) in Phase 2, defined as the time (days) from the date of randomization to the date of the first on-study SSE [ Time Frame: Up to 25 months ]
  6. Symptomatic skeletal event free survival in Phase 2, 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 [ Time Frame: Up to 25 months ]
  7. Time to pain progression in Phase 2 [ Time Frame: Up to 25 months ]
  8. Duration of response in Phase 2 [ Time Frame: Up to 25 months ]
  9. Objective Response Rate (ORR) in Phase 2 [ Time Frame: Up to 25 months ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Cytologically or histologically confirmed diagnosis of multiple myeloma
  • 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
  • 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
    • Urine M-protein ≥200 mg/24 hours
    • Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio
  • ≥1 bone lesion identifiable by radiograph, computed tomography, magnetic resonance imaging, or bone scintigraphy
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
  • Subjects must be nonrefractory to bortezomib and had no progression during or within 60 days after completion of bortezomib
  • 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)

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 ≤10 mg/day 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
  • Systemic anti-cancer therapy within 4 weeks prior to first dose
  • 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): NCT02605356


Locations
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Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02605356    
Other Study ID Numbers: 17451
2015-000427-82 ( EudraCT Number )
First Posted: November 16, 2015    Key Record Dates
Last Update Posted: October 7, 2016
Last Verified: September 2016
Keywords provided by Bayer:
Radium-223 dichloride
bortezomib
dexamethasone
early relapsed multiple myeloma
combination therapy multiple myeloma
Additional relevant MeSH terms:
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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
Bortezomib
Radium Ra 223 dichloride
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