stop_circleTerminated/Withdrawn

Multiple Myeloma

Bayer Identifier:

17451

ClinicalTrials.gov Identifier:

NCT02605356

EudraCT Number:

2015-000427-82

EU CT Number:

Not Available
Phase 1b/2 study testing radium-223 dichloride/bortezomib/dexamethasone combination in relapsed multiple myeloma

Trial purpose

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.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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)
  • - 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

Trial summary

Enrollment Goal
0
Trial Dates
October 2016 - July 2021
Phase
Phase 1/Phase 2
Could I Receive a placebo
Yes
Products
Xofigo (Radium-223 dichloride, BAY88-8223)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Terminated
Encinitas, 92024, United States
Terminated
New York, 10032-3729, United States
Terminated
Torino, 10126, Italy
Terminated
Novara, 28100, Italy
Terminated
Watertown, 57201, United States
Terminated
Jerusalem, 9112001, Israel
Terminated
Afula, 1834111, Israel
Terminated
Haifa, 31048, Israel
Terminated
Ramat Gan, 5262000, Israel
Terminated
Zerifin, 6093000, Israel
Terminated
Athens, 11528, Greece
Terminated
Rio / Patra, 26500, Greece
Terminated
Milano, 20089, Italy
Terminated
BRUXELLES - BRUSSEL, 1090, Belgium
Terminated
BRUGGE, 8000, Belgium
Terminated
YVOIR, 5530, Belgium
Terminated
LIEGE, 4000, Belgium
Terminated
Bologna, 40138, Italy
Terminated
Milano, 20132, Italy
Terminated
Firenze, 50141, Italy
Terminated
Quebec, G1R 2J6, Canada
Terminated
München, 81377, Germany
Terminated
Tübingen, 72076, Germany
Terminated
Berlin, 12203, Germany
Terminated
Mainz, 55131, Germany
Terminated
BRUXELLES - BRUSSEL, 1200, Belgium
Terminated
Winston-Salem, 27157, United States
Terminated
Barcelona, 08035, Spain
Terminated
Barcelona, 08036, Spain
Terminated
Valencia, 46017, Spain
Terminated
Palma de Mallorca, 07010, Spain
Terminated
Madrid, 28046, Spain
Terminated
Madrid, 28006, Spain
Terminated
San Sebastián, 20014, Spain
Terminated
Sevilla, 41013, Spain
Terminated
Seattle, 98104, United States
Terminated
Seoul, 03080, Korea, Republic Of
Terminated
Seoul, 137-701, Korea, Republic Of
Terminated
Scottsdale, 85259-5404, United States
Terminated
Pisa, 56126, Italy
Terminated
Cagliari, 09121, Italy
Terminated
Durham, 27710, United States
Terminated
Taipei, 10016, Taiwan
Terminated
Taipei, 11217, Taiwan
Terminated
Taichung, 40447, Taiwan
Terminated
Taipei, Taiwan
Terminated
Taipei, Taiwan
Terminated
Daegu, 700-701, Korea, Republic Of
Terminated
Goyang-si, 410-769, Korea, Republic Of
Terminated
Seoul, 138-736, Korea, Republic Of
Terminated
Little Rock, 72205, United States
Terminated
Rockville, 20850-6535, United States
Terminated
Metairie, 70006, United States
Terminated
Jeollanam-do, 519-763, Korea, Republic Of
Terminated
Seoul, 135-710, Korea, Republic Of
Terminated
Badalona, 08916, Spain
Terminated
Reggio Emilia, 42123, Italy
Terminated
BOX HILL, 3128, Australia
Terminated
Adelaide, 5000, Australia

Primary Outcome

  • Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)
    date_rangeTime Frame:
    At 13 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • 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)
    date_rangeTime Frame:
    Approximately 12 months
    enhanced_encryption
    Safety Issue:
    No
  • 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
    date_rangeTime Frame:
    Approximately 12 months
    enhanced_encryption
    Safety Issue:
    No
  • Number of participants with adverse events in phase 2
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No
  • 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
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No
  • 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
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No
  • Time to pain progression in Phase 2
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No
  • Duration of response in Phase 2
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No
  • Objective Response Rate (ORR) in Phase 2
    date_rangeTime Frame:
    Up to 25 months
    enhanced_encryption
    Safety Issue:
    No

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
5

Additional Information

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