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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.

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ClinicalTrials.gov Identifier: NCT00726869
Recruitment Status : Terminated (Enrollment has been halted)
First Posted : August 1, 2008
Last Update Posted : August 23, 2012
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Abbott

July 29, 2008
August 1, 2008
August 23, 2012
May 2008
March 2012   (Final data collection date for primary outcome measure)
  • Identify the maximum tolerated dose of elotuzumab in combination with bortezomib (phase 1). [ Time Frame: First cycle of treatment. ]
    The highest dose level of elotuzumab at which <= 1 dose-limiting toxicity occurs in 6 subjects
  • Evaluate the efficacy of elotuzumab in combination with bortezomib (phase 2). [ Time Frame: Screening to the 30 day follow up visit. ]
    Objective response rate (complete and partial response) according to European Group for Blood and Marrow Transplantation (EBMT) criteria
The incidence of dose-limiting toxicities in the first treatment cycle foreach 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. ]
Complete list of historical versions of study NCT00726869 on ClinicalTrials.gov Archive Site
  • Evaluate the efficacy of elotuzumab in combination with bortezomib (phase 1). [ Time Frame: Screening to the 30 day follow up visit. ]
    Objective response rate according to EBMT criteria, duration of response, time to progression, and progression-free survival
  • Evaluate the safety of elotuzumab in combination with bortezomib (phase 1 and 2). [ Time Frame: Screening to the 30 day follow up visit. ]
    Frequency, severity, and relationship of adverse events and serious adverse events with the combination of elotuzumab and bortezomib
  • Evaluate the pharmacokinetic parameters of elotuzumab in combination with bortezomib (phase 1 and 2) [ Time Frame: Screening to the 30 day follow up visit. ]
    Pharmacokinetic profile
  • Evaluate the immunogenicity of elotuzumab in combination with bortezomib (phase 1 and 2). [ Time Frame: Screening to the 30 day follow up visit. ]
    Incidence of elotuzumab-specific antidrug antibodies
  • Evaluate the pharmacodynamics of elotuzumab in combination with bortezomib (phase 1 and 2). [ Time Frame: Screening to the 30 day follow up visit. ]
    Changes in pharmacodynamic endpoints as they relate to dose, response, and toxicity of elotuzumab in combination with bortezomib
Frequency, severity, and relationship of adverse events and serious adverse events with the combination of HuLuc63 and bortezomib. [ Time Frame: After 3 patients are enrolled into each of the 4 cohorts and have completed the first cycle of treatment within the cohort. ]
Not Provided
Not Provided
 
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.
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.
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).
The phase 2 portion of this study was not initiated because a decision was made to conduct a phase 2 randomized clinical trial.
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Multiple Myeloma
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 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 Name: Elotuzumab
  • Experimental: Cohort 1
    2.5 mg/kg
    Intervention: Drug: Elotuzumab (HuLuc63)
  • Experimental: Cohort 2
    5.0 mg/kg
    Intervention: Drug: Elotuzumab (HuLuc63)
  • Experimental: Cohort 3
    10.0 mg/kg
    Intervention: Drug: Elotuzumab (HuLuc63)
  • Experimental: Cohort 4
    20.0 mg/kg
    Intervention: Drug: Elotuzumab (HuLuc63)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
28
49
March 2012
March 2012   (Final data collection date for primary outcome measure)

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.
  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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00726869
HuLuc63-1702
Yes
Not Provided
Not Provided
Abbott
Abbott
Bristol-Myers Squibb
Study Director: Anil Singhal, PhD Abbott
Abbott
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP