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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. (HuLuc63-1702)
This study is ongoing, but not recruiting participants.

First Received on July 29, 2008.   Last Updated on August 30, 2011   History of Changes
Sponsor: Facet Biotech
Collaborator: Bristol-Myers Squibb
Information provided by (Responsible Party): Facet Biotech
ClinicalTrials.gov Identifier: NCT00726869
  Purpose

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 (ie, Days 1 and 11).


Condition Intervention Phase
Multiple Myeloma
Drug: Elotuzumab (HuLuc63)
Phase I
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Facet Biotech:

Primary Outcome Measures:
  • The incidence of dose-limiting toxicities in the first treatment cycle for each cohort. [ Time Frame: After 3 patients are enrolled into each of the 4 cohorts and have completed the first cycle of treatment within the cohort. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 1) Frequency, severity, and relationship of adverse events and serious adverse events with the combination of elotuzumab and bortezomib. 2) Overall response rate (for Phase 1), time to progression, and progression-free survival. 3) Pharmacokinetic prof [ Time Frame: After 3 patients are enrolled into each of the 4 cohorts and have completed the first cycle of treatment within the cohort. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 49
Study Start Date: October 2007
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: elotuzumab
Various concentrations of elotuzumab (2.5 mg/kg; 5.0 mg/kg; 10.0 mg/kg; and 20.0 mg/kg)
Drug: Elotuzumab (HuLuc63)
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 with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8; and Cohort 4 - 20.0 mg/kg HuLuc63 IV with bortezomib on Days 1 & 11, with only Bortezomib IV on Days 4 & 8.
Other Name: Elotuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, age 18 years or older.
  2. Diagnosis of MM and documentation of 1 to 3 prior therapies.
  3. 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.
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix E).
  5. 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.
  6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN).
  7. Total bilirubin ≤2 x ULN.
  8. Serum creatinine ≤2.0 mg/dL (unless related to MM, then ≤3.0 mg/dL).
  9. 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;
  10. 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.
  11. Use of appropriate contraception where applicable.
  12. Negative urine pregnancy test where applicable.
  13. Must have 2-dimensional echocardiogram indicating left ventricular ejection fraction (LVEF) ≥45% within 30 days prior to the first dose of elotuzumab.
  14. 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:

  1. Life expectancy of less than 3 months.
  2. 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.
  3. 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.
  4. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
  5. Prior treatment with bortezomib in 3 months prior to the first dose.
  6. 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.
  7. Prior therapy with anti-CD56+ therapeutics.
  8. Radiotherapy within 2 weeks prior to the first dose of elotuzumab.
  9. Investigational drug within 3 weeks or 3x the half-life of the investigational drug (whichever is longer )of the first dose of elotuzumab.
  10. Prior peripheral stem cell transplant within 12 weeks of the first dose of elotuzumab.
  11. Nitrogen mustard agents, melphalan, or monoclonal antibodies within 6 weeks of the first dose of elotuzumab.
  12. Neuropathy ≥Grade 2 (NCI CTCAE v3.0).
  13. Current orthostatic hypotension.
  14. Known active infections requiring antibiotic, antiviral, or antifungal therapy.
  15. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
  16. Any condition that in the investigator's opinion makes the subject unsuitable for study participation.
  17. Hypersensitivity to recombinant proteins or excipients in elotuzumab or bortezomib.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00726869

Locations
United States, California
USC/Norris Cancer Center
Los Angeles, California, United States, 90033
United States, Illinois
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637-1470
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-5936
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Facet Biotech
Bristol-Myers Squibb
  More Information

No publications provided

Responsible Party: Facet Biotech
ClinicalTrials.gov Identifier: NCT00726869     History of Changes
Other Study ID Numbers: HuLuc63-1702
Study First Received: July 29, 2008
Last Updated: August 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Facet Biotech:
Patients
After
One to three
Prior
Therapies

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012