Multiple MyelomaPhase 1/2NCT02928029
Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma
A Phase 1/2 study testing Radium-223 dichloride (Xofigo, BAY88-8223), Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Bayer at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Radium-223 dichloride (Xofigo, BAY88-8223), Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 10 Feb 2017to 20 Mar 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States3 sites
Pacific Oncology/Hematology Associates
Encinitas, California, 92024
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4417
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
South Korea2 sites
National Cancer Center
Goyang-si, Gyeonggido, 410-769
Seoul National University Hospital
Seoul, 03080
Spain2 sites
Hospital Universitari Son Espases
Palma de Mallorca, Illes Baleares, 07120
Hospital Universitario Virgen del Rocío
Seville, 41013
About this study
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
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 12 subjects in all dose cohorts combined will be treated in the phase 1b part of the study. Up to approximately 100 subjects will be enrolled in the phase 2 part of the study.
- Conditions
- Multiple Myeloma
- Being tested
- Radium-223 dichloride (Xofigo, BAY88-8223), Placebo, Bortezomib, Dexamethasone
- Keywords
- Radium-223 dichloride, Bortezomib, Dexamethasone, Relapsed multiple myeloma, Combination therapy multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radium-223 dichloride (Xofigo, BAY88-8223)Drug
Sequential dose escalation in Intravenous (IV) injection
PlaceboDrug
Matching placebo
BortezomibDrug
Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose
DexamethasoneDrug
Dexamethasone is administered orally at 40 mg
| Study group | Role | What they receive |
|---|---|---|
| Phase1, arm1: 33 kBq/kg Radium-223 dichloride+SOC | Experimental | 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. Receives: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Bortezomib; Drug: Dexamethasone |
| Phase1, arm2: 55 kBq/kg Radium-223 dichloride+SOC | Experimental | 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. Receives: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Bortezomib; Drug: Dexamethasone |
| Phase2, arm1: Placebo+SOC | Placebo comparator | Phase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone. Receives: Drug: Placebo; Drug: Bortezomib; Drug: Dexamethasone |
| Phase2, arm2: Radium-223 dichloride+SOC | Experimental | Phase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone Receives: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: MTD/RP2D Determined by the Incidence of DLTs
Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for the severity grade
Measured: From the start of study medication through 3 weeks after administration of the second dose of radium-223 dichloride, assessed up to 9 weeks
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Drug-related TEAEs, and Treatment-emergent Serious AE
A treatment-emergent adverse event (TEAE) is defined as any event arising or worsening after start of study drug administration until the end of the treatment period
Measured: From the start of study drug (radium-223 dichloride) to 30 days after last dose of study treatment (radium-223 dichloride, BOR, or DEX, whichever is last), assessed up to approximately 2 years
Secondary outcomes (1)
Phase 1: The Number of Subjects With Complete Response (CR) and Very Good Partial Response (VGPR)
Determined by International Myeloma Working Group (IMWG) uniform response criteria.
CR: Negative immunofixation of serum and urine, disappearance of any soft-tissue plasmacytomas, and <5% plasma cells in bone marrow; in patients for whom only measurable disease is by serum free light chain (FLC) level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required; 2 consecutive assessments are needed.
VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component <100 mg/24 hours (hrs); in patients for whom only measurable disease is by serum FLC level, >90% decrease in difference between involved and uninvolved FLC levels, in addition to VGPR criteria, is required; 2 consecutive assessments are needed
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2016 (estimated)
- Study start10 Feb 2017
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Why it stopped: Due to the changes of standard of care and the slow recruitment of participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02928029
- Sponsor's protocol ID
- 18987
- Other IDs
- 2016-002438-58, 2016
- Status last verified
- Feb 2020
- First submitted
- 6 Oct 2016
- Last updated
- 26 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02928029
- Acronym / sponsor ID
- 18987
- Conditions
- Multiple Myeloma
- Keywords
- Radium-223 dichloride, Bortezomib, Dexamethasone, Relapsed multiple myeloma, Combination therapy multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the changes of standard of care and the slow recruitment of participants.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 10 Feb 2017 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 7 Oct 2016 (estimated)
- Results
- Posted 26 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 12 subjects in all dose cohorts combined will be treated in the phase 1b part of the study. Up to approximately 100 subjects will be enrolled in the phase 2 part of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase1, arm1: 33 kBq/kg Radium-223 dichloride+SOC | Experimental | Drug: Radium-223 dichloride (Xofigo, BAY88-8223), Drug: Bortezomib, Drug: DexamethasonePhase 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. |
| Phase1, arm2: 55 kBq/kg Radium-223 dichloride+SOC | Experimental | Drug: Radium-223 dichloride (Xofigo, BAY88-8223), Drug: Bortezomib, Drug: DexamethasonePhase 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. |
| Phase2, arm1: Placebo+SOC | Placebo comparator | Drug: Placebo, Drug: Bortezomib, Drug: DexamethasonePhase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone. |
| Phase2, arm2: Radium-223 dichloride+SOC | Experimental | Drug: Radium-223 dichloride (Xofigo, BAY88-8223), Drug: Bortezomib, Drug: DexamethasonePhase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radium-223 dichloride (Xofigo, BAY88-8223)Sequential dose escalation in Intravenous (IV) injection | Drug | Phase1, arm1: 33 kBq/kg Radium-223 dichloride+SOC, Phase1, arm2: 55 kBq/kg Radium-223 dichloride+SOC, Phase2, arm2: Radium-223 dichloride+SOC |
| PlaceboMatching placebo | Drug | Phase2, arm1: Placebo+SOC |
| BortezomibBortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose | Drug | 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 |
| DexamethasoneDexamethasone is administered orally at 40 mg | Drug | 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 |
Primary outcome
Phase 1: MTD/RP2D Determined by the Incidence of DLTs
Time frame: From the start of study medication through 3 weeks after administration of the second dose of radium-223 dichloride, assessed up to 9 weeks
Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for the severity grade
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Drug-related TEAEs, and Treatment-emergent Serious AE
Time frame: From the start of study drug (radium-223 dichloride) to 30 days after last dose of study treatment (radium-223 dichloride, BOR, or DEX, whichever is last), assessed up to approximately 2 years
A treatment-emergent adverse event (TEAE) is defined as any event arising or worsening after start of study drug administration until the end of the treatment period
1 secondary outcome
Phase 1: The Number of Subjects With Complete Response (CR) and Very Good Partial Response (VGPR)
Time frame: Up to approximately 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Multiple Myeloma
RecruitingPhase 1/2
A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma
Relapsed/Refractory Multiple Myeloma
RecruitingPhase 1
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Malignancy, Hematologic, Neoplasms, Hematologic
RecruitingObservational study
Screening for AL Amyloidosis in Smoldering Multiple Myeloma
Smoldering Multiple Myeloma
RecruitingPhase 1/2
Study of Carfilzomib, Lenalidomide, Dexamethasone and Belantamab Mafodotin in Multiple Myeloma
Multiple Myeloma
RecruitingObservational study
Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols
Multiple Myeloma, Lymphoma, Non-Hodgkin
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Radium-223 dichloride (Xofigo, BAY88-8223), Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Bayer at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, South Korea, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: MTD/RP2D Determined by the Incidence of DLTs (time frame: From the start of study medication through 3 weeks after administration of the second dose of radium-223 dichloride, assessed up to 9 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2020.