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 study has been terminated.
(Enrollment has been halted)
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00726869
First received: July 29, 2008
Last updated: August 22, 2012
Last verified: June 2012
  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 (i.e., Days 1 and 11).


Condition Intervention Phase
Multiple Myeloma
Drug: Elotuzumab (HuLuc63)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-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 Abbott:

Primary Outcome Measures:
  • Identify the maximum tolerated dose of elotuzumab in combination with bortezomib (phase 1). [ Time Frame: First cycle of treatment. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
    Objective response rate (complete and partial response) according to European Group for Blood and Marrow Transplantation (EBMT) criteria


Secondary Outcome Measures:
  • Evaluate the efficacy of elotuzumab in combination with bortezomib (phase 1). [ Time Frame: Screening to the 30 day follow up visit. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    Changes in pharmacodynamic endpoints as they relate to dose, response, and toxicity of elotuzumab in combination with bortezomib


Enrollment: 28
Study Start Date: May 2008
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
2.5 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 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 2
5.0 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 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 3
10.0 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 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 4
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 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

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.

  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.
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00726869

Locations
United States, California
Site Reference ID/Investigator# 63853
Los Angeles, California, United States, 90033
United States, Illinois
Site Reference ID/Investigator# 63855
Chicago, Illinois, United States, 60637
United States, Massachusetts
Site Reference ID/Investigator# 63847
Boston, Massachusetts, United States, 02115
United States, Michigan
Site Reference ID/Investigator# 63852
Ann Arbor, Michigan, United States, 48109-5936
United States, New Jersey
Site Reference ID/Investigator# 63854
Hackensack, New Jersey, United States, 07601
United States, New York
Site Reference ID/Investigator# 63850
Buffalo, New York, United States, 14263
United States, Ohio
Site Reference ID/Investigator# 63849
Columbus, Ohio, United States, 43210
United States, Washington
Site Reference ID/Investigator# 63848
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Abbott
Bristol-Myers Squibb
Investigators
Study Director: Anil Singhal, PhD Abbott
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00726869     History of Changes
Other Study ID Numbers: HuLuc63-1702
Study First Received: July 29, 2008
Last Updated: August 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Abbott:
Patients After One to three Prior Therapies

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

ClinicalTrials.gov processed this record on October 30, 2014