Clinical trial NCT00775502: Phase 1/2 Study of Anti GM-2 Monoclonal Antibody To Treat Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
GM-2 ganglioside
monoclonal antibody
Potelligent design
Treatment of subjects who have failed previous treatment
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kirin Pharma, Inc.
First posted: 2008-10-20
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum M protein levels
timeFrame: one month
Secondary outcomes:
measure: Time to progression or death
timeFrame: 6 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Durham
country: United States
facility: Duke Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Taussig Cancer Center- Cleveland Clinic
state: Ohio
Study officials:
affiliation: Karmanos Cancer Center
name: Jeffrey Zonder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baz RC, Zonder JA, Gasparetto C, Reu FJ, Strout V. Phase I Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Patients with Previously Treated Multiple Myeloma. Oncol Ther. 2016;4(2):287-301. doi: 10.1007/s40487-016-0034-y. Epub 2016 Nov 2.