Clinical trial NCT02605356: Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Radium-223 dichloride
bortezomib
dexamethasone
early relapsed multiple myeloma
combination therapy multiple myeloma
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-11-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)
timeFrame: At 13 months
measure: Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression
timeFrame: Up to 25 months
Secondary outcomes:
measure: 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)
timeFrame: Approximately 12 months
measure: 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
timeFrame: Approximately 12 months
measure: Number of participants with adverse events in phase 2
timeFrame: Up to 25 months
measure: Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause
timeFrame: Up to 25 months
measure: 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
timeFrame: Up to 25 months
measure: 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
timeFrame: Up to 25 months
measure: Time to pain progression in Phase 2
timeFrame: Up to 25 months
measure: Duration of response in Phase 2
timeFrame: Up to 25 months
measure: Objective Response Rate (ORR) in Phase 2
timeFrame: Up to 25 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Encinitas
country: United States
state: California
city: Metairie
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Watertown
country: United States
state: South Dakota
city: Seattle
country: United States
state: Washington
city: Adelaide
country: Australia
state: South Australia
city: Box Hill
country: Australia
city: Brugge
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Liege
country: Belgium
city: Yvoir
country: Belgium
city: Quebec
country: Canada
city: Tübingen
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Berlin
country: Germany
city: Athens
country: Greece
city: Rio / Patra
country: Greece
city: Afula
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Zerifin
country: Israel
city: Bologna
country: Italy
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
state: Emilia-Romagna
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Novara
country: Italy
state: Piemonte
city: Torino
country: Italy
state: Piemonte
city: Cagliari
country: Italy
state: Sardegna
city: Firenze
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Goyang-si
country: Korea, Republic of
state: Gyeonggido
city: Daegu
country: Korea, Republic of
city: Jeollanam-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Badalona
country: Spain
state: Barcelona
city: San Sebastián
country: Spain
state: Guipúzcoa
city: Palma de Mallorca
country: Spain
state: Illes Baleares
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: