- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00726869
A Phase 1/2, Multi-center, Open-label, Dose-escalation Study of Elotuzumab(Humanized Anti-CS1 Monoclonal IgG1 Antibody) and Bortezomib in Subjects With Multiple Myeloma Following One to Three Prior Therapies.
August 22, 2012 updated by: Abbott
This Phase 1/2, multi-center, open-label, multiple-dose, dose escalation study will evaluate the combination of elotuzumab and bortezomib in subjects with MM following 1 to 3 prior therapies.
For the Phase 1 portion, elotuzumab will be administered by intravenous (IV) infusion at up to 4 dose levels ranging from 2.5 mg/kg to 20.0 mg/kg within 30 minutes following the administration of bortezomib at 1.3 mg/m^2 IV bolus.
Bortezomib will be given in 21 day cycles (twice weekly for 2 weeks on Days 1, 4, 8, and 11 followed by a 10-day rest period).
Elotuzumab will be administered as a separate infusion within 30 minutes following bortezomib administration on the same days as the first and last dose of each bortezomib cycle (i.e., Days 1 and 11).
Study Overview
Detailed Description
The phase 2 portion of this study was not initiated because a decision was made to conduct a phase 2 randomized clinical trial.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90033
- Site Reference ID/Investigator# 63853
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Illinois
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Chicago, Illinois, United States, 60637
- Site Reference ID/Investigator# 63855
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Site Reference ID/Investigator# 63847
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Michigan
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Ann Arbor, Michigan, United States, 48109-5936
- Site Reference ID/Investigator# 63852
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Site Reference ID/Investigator# 63854
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New York
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Buffalo, New York, United States, 14263
- Site Reference ID/Investigator# 63850
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Ohio
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Columbus, Ohio, United States, 43210
- Site Reference ID/Investigator# 63849
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Washington
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Seattle, Washington, United States, 98109
- Site Reference ID/Investigator# 63848
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria
- Males or females, age 18 years or older.
- Diagnosis of MM and documentation of 1 to 3 prior therapies.
- M-protein spike (complete immunoglobulin molecule) of >= 1g/dL in serum and/or >= 0.5 g excreted in a 24-hour urine collection sample. Light chain only disease is not an inclusion criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- No prior bortezomib treatment OR responsive (PR or better) to prior bortezomib treatment for a minimum of 3 months OR responsive to prior bortezomib treatment at the time of going to another treatment or ceasing treatment.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <=3 x upper limit of normal (ULN).
- Total bilirubin <=2 x ULN.
- Serum creatinine <=2.0 mg/dL (unless related to MM, then <=3.0 mg/dL).
Must have adequate bone marrow function defined as:
- Absolute neutrophil count >1,000 cells/mm3 (1.0 x 10^9 cells/L) without growth factor support for 7 days;
- Platelets >=75,000 cells/mm3 (75 x 10^9 cells/L) without transfusion within 72 hours of screening;
- Hemoglobin >=8 g/dL without red blood cell transfusion within 2 weeks of screening;
- Serum calcium (corrected for albumin) level at or below ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment); additional screening time may be allowed for confirmation - consult with sponsor's medical monitor.
- Use of appropriate contraception where applicable.
- Negative urine pregnancy test where applicable.
- Must have 2-dimensional echocardiogram indicating left ventricular ejection fraction (LVEF) >=45% within 30 days prior to the first dose of elotuzumab.
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
Exclusion Criteria
- Life expectancy of less than 3 months.
- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years.
- Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary,(including acute diffuse infiltrative pulmonary and pericardial disease), hepatic, and renal diseases unless renal insufficiency is felt to be secondary to MM.
- Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
- Prior treatment with bortezomib in 3 months prior to the first dose.
- Thalidomide, lenalidomide cytotoxic chemotherapy, or corticosteroids (except prior to infusion of first dose of study drug as prophylaxis for infusion reactions) within 2 weeks of the first dose of elotuzumab.
- Prior therapy with anti-CD56+ therapeutics.
- Radiotherapy within 2 weeks prior to the first dose of elotuzumab.
- Investigational drug within 3 weeks or 3x the half-life of the investigational drug (whichever is longer ) of the first dose of elotuzumab.
- Prior peripheral stem cell transplant within 12 weeks of the first dose of elotuzumab.
- Nitrogen mustard agents, melphalan, or monoclonal antibodies within 6 weeks of the first dose of elotuzumab.
- Neuropathy >=Grade 2 (NCI CTCAE v3.0).
- Current orthostatic hypotension.
- Known active infections requiring antibiotic, antiviral, or antifungal therapy.
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
- Any condition that in the investigator's opinion makes the subject unsuitable for study participation.
- Hypersensitivity to recombinant proteins or excipients in elotuzumab or bortezomib.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort 1
2.5 mg/kg
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Cohort 1 - 2.5 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 2 - 5.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 3 - 10.0 mg/kg elotuzumab IV withbortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; and Cohort 4 - 20.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8.
Other Names:
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Experimental: Cohort 2
5.0 mg/kg
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Cohort 1 - 2.5 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 2 - 5.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 3 - 10.0 mg/kg elotuzumab IV withbortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; and Cohort 4 - 20.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8.
Other Names:
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Experimental: Cohort 3
10.0 mg/kg
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Cohort 1 - 2.5 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 2 - 5.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 3 - 10.0 mg/kg elotuzumab IV withbortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; and Cohort 4 - 20.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8.
Other Names:
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Experimental: Cohort 4
20.0 mg/kg
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Cohort 1 - 2.5 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 2 - 5.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; Cohort 3 - 10.0 mg/kg elotuzumab IV withbortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; and Cohort 4 - 20.0 mg/kg elotuzumab IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Identify the maximum tolerated dose of elotuzumab in combination with bortezomib (phase 1).
Time Frame: First cycle of treatment.
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The highest dose level of elotuzumab at which <= 1 dose-limiting toxicity occurs in 6 subjects
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First cycle of treatment.
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Evaluate the efficacy of elotuzumab in combination with bortezomib (phase 2).
Time Frame: Screening to the 30 day follow up visit.
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Objective response rate (complete and partial response) according to European Group for Blood and Marrow Transplantation (EBMT) criteria
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Screening to the 30 day follow up visit.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate the efficacy of elotuzumab in combination with bortezomib (phase 1).
Time Frame: Screening to the 30 day follow up visit.
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Objective response rate according to EBMT criteria, duration of response, time to progression, and progression-free survival
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Screening to the 30 day follow up visit.
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Evaluate the safety of elotuzumab in combination with bortezomib (phase 1 and 2).
Time Frame: Screening to the 30 day follow up visit.
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Frequency, severity, and relationship of adverse events and serious adverse events with the combination of elotuzumab and bortezomib
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Screening to the 30 day follow up visit.
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Evaluate the pharmacokinetic parameters of elotuzumab in combination with bortezomib (phase 1 and 2)
Time Frame: Screening to the 30 day follow up visit.
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Pharmacokinetic profile
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Screening to the 30 day follow up visit.
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Evaluate the immunogenicity of elotuzumab in combination with bortezomib (phase 1 and 2).
Time Frame: Screening to the 30 day follow up visit.
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Incidence of elotuzumab-specific antidrug antibodies
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Screening to the 30 day follow up visit.
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Evaluate the pharmacodynamics of elotuzumab in combination with bortezomib (phase 1 and 2).
Time Frame: Screening to the 30 day follow up visit.
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Changes in pharmacodynamic endpoints as they relate to dose, response, and toxicity of elotuzumab in combination with bortezomib
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Screening to the 30 day follow up visit.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Anil Singhal, PhD, Abbott
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2008
Primary Completion (Actual)
March 1, 2012
Study Completion (Actual)
March 1, 2012
Study Registration Dates
First Submitted
July 29, 2008
First Submitted That Met QC Criteria
July 30, 2008
First Posted (Estimate)
August 1, 2008
Study Record Updates
Last Update Posted (Estimate)
August 23, 2012
Last Update Submitted That Met QC Criteria
August 22, 2012
Last Verified
June 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Antineoplastic Agents
- Elotuzumab
Other Study ID Numbers
- HuLuc63-1702
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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