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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02605356
• Other study ID #: 17451
• Secondary ID: 2015-000427-82
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: November 12, 2015
• Last updated: October 6, 2016
• Start date: October 2016
• Est. completion date: July 2021

Study information

• Verified date: September 2016
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Ministry of Social Affairs, Public Health and the EnvironmentCanada: Health CanadaCzech Republic: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesGreece: Ministry of Health and WelfareIsrael: Ministry of HealthItaly: Ministry of HealthJapan: Pharmaceuticals and Medical Devices AgencyKorea: Ministry of Food and Drug SafetyNew Zealand: MedsafePoland: Ministry of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosTaiwan: Department of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2021
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Radium-223 dichloride (Xofigo, BAY88-8223)

• Placebo

• Bortezomib

• Dexamethasone

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)		At 13 months	Yes
Primary	Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression		Up to 25 months	No
Secondary	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)		Approximately 12 months	No
Secondary	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		Approximately 12 months	No
Secondary	Number of participants with adverse events in phase 2		Up to 25 months	Yes
Secondary	Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause		Up to 25 months	No
Secondary	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		Up to 25 months	No
Secondary	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		Up to 25 months	No
Secondary	Time to pain progression in Phase 2		Up to 25 months	No
Secondary	Duration of response in Phase 2		Up to 25 months	No
Secondary	Objective Response Rate (ORR) in Phase 2		Up to 25 months	No

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