Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma

NCT02928029 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 189872016-002438-58
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 7

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 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

Keywords

Radium-223 dichloride; Bortezomib; Dexamethasone; Relapsed multiple myeloma; Combination therapy multiple myeloma

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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)

  Up to approximately 2 years

Study Arms (4)

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.

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.

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.

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

Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Bortezomib; Drug: Dexamethasone

Interventions

Radium-223 dichloride (Xofigo, BAY88-8223) DRUG

Sequential dose escalation in Intravenous (IV) injection

Phase1, arm1: 33 kBq/kg Radium-223 dichloride+SOC; Phase1, arm2: 55 kBq/kg Radium-223 dichloride+SOC; Phase2, arm2: Radium-223 dichloride+SOC

Placebo DRUG

Matching placebo

Phase2, arm1: Placebo+SOC

Bortezomib DRUG

Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose

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

Dexamethasone DRUG

Dexamethasone is administered orally at 40 mg

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

Pacific Oncology/Hematology Associates

Encinitas, California, 92024, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4417, United States

Location

National Cancer Center

Goyang-si, Gyeonggido, 410-769, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitari Son Espases

Palma de Mallorca, Illes Baleares, 07120, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Related Links

• Click here to find results for studies related to Bayer products

MeSH Terms

Conditions

Multiple Myeloma

Interventions

radium Ra 223 dichloride; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 7, 2016
• Study Start: February 10, 2017
• Primary Completion: March 20, 2019
• Study Completion: March 20, 2019
• Last Updated: February 26, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-02

Locations

KR (2); ES (2); US (3)