Phase 1/2 Study of Anti GM-2 Monoclonal Antibody To Treat Multiple Myeloma

Study Overview
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Brief Summary
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This study will test the ability of a specially designed monoclonal antibody to destroy multiple myeloma cells. This antibody is unique in its ability to promote the death of multiple myeloma cells by processes known as antibody dependent cellular cytotoxicity (ADCC)and complement dependent cytotoxicity (CDC). The study is designed to determine both the optimal dose of the antibody to destroy multiple myeloma cells and frequency of dosing.

Detailed Description
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BIW-8962 is a monoclonal antibody which targets the GM-2 ganglioside which is expressed at high levels on the surface of multiple myeloma cells. This is a Phase 1/2 study design. The Phase 1 component will establish the active biologic dose (ABD) or the maximum tolerated dose (MTD) as well as the appropriate dosing frequency based on the pharmacokinetics of the antibody and approximately 45 subjects will be enrolled in this part of the study. The initial dosing frequency will be every two weeks and the doses to be tested will range from 0.03 mg/kg to 10 mg/kg. Once the recommended Phase 2 dose and frequency have been established in Phase 1, the efficacy of the drug will be investigated in approximately 35 subjects in Phase 2. The study did not proceed beyond the Phase 1a portion. On 30 Nov 2010, Kyowa Hakko Kirin Pharma, Inc. (KKP) notified Investigators of the decision to terminate BIW-8962-001 due to a lack of efficacy in Multiple Myeloma. The Phase 1 Part B and the Phase 2 components of the study were not conducted. The study was terminated and summarized in an abbreviated clinical study report (submitted 26 June 2012; SN045). Kyowa Kirin Pharma has no current plans to pursue the use of BIW8962 in multiple myeloma.

Official Title
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Open-Label, Multi-Center, Dose Escalation Phase 1/2 Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Subjects With Previously Treated Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: BIW-8962


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory myeloma M-protein in serum and/or urine by IMWG criteria. Bone marrow plasma cells or plasmacytoma Related organ or tissue impairment (CRAB) Subjects without detectable M protein are eligible if they have an abnormal serum free light chain ratio (FLC) or if they have at least 10% plasma cells in the bone marrow Exclusion Criteria: Ongoing infection Cardiac disease Uncontrolled hypertension Active liver disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIW-8962, monoclonal antibody<br> | Drug: BIW-8962<br>* Intravenous administration of liquid dosage form. Doses 0.03, 0.10, 0.30, 1.0, 3.0, and 10 mg/kg. Frequency is once every two weeks. Duration is 6 months<br>* Other names: anti GM2 monoclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum M protein levels |  | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression or death |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, GM-2 ganglioside, monoclonal antibody, Potelligent design, Treatment of subjects who have failed previous treatment