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.

NCT ID: NCT00726869

Last Updated: 2012-08-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2012-03-31

Brief Summary

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).

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.

Conditions

Multiple Myeloma

Keywords

Patients After One to three Prior Therapies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

2.5 mg/kg

Group Type: EXPERIMENTAL

Elotuzumab (HuLuc63)

Intervention Type: DRUG

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.

Cohort 2

5.0 mg/kg

Group Type: EXPERIMENTAL

Elotuzumab (HuLuc63)

Intervention Type: DRUG

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.

Cohort 3

10.0 mg/kg

Group Type: EXPERIMENTAL

Elotuzumab (HuLuc63)

Intervention Type: DRUG

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.

Cohort 4

20.0 mg/kg

Group Type: EXPERIMENTAL

Elotuzumab (HuLuc63)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Elotuzumab

Eligibility Criteria

Inclusion Criteria

1. Males or females, age 18 years or older.

2. Diagnosis of MM and documentation of 1 to 3 prior therapies.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anil Singhal, PhD

Role: STUDY_DIRECTOR

Abbott

Locations

Site Reference ID/Investigator# 63853

Los Angeles, California, United States

Site Reference ID/Investigator# 63855

Chicago, Illinois, United States

Site Reference ID/Investigator# 63847

Boston, Massachusetts, United States

Site Reference ID/Investigator# 63852

Ann Arbor, Michigan, United States

Site Reference ID/Investigator# 63854

Hackensack, New Jersey, United States

Site Reference ID/Investigator# 63850

Buffalo, New York, United States

Site Reference ID/Investigator# 63849

Columbus, Ohio, United States

Site Reference ID/Investigator# 63848

Seattle, Washington, United States

Countries

United States

Other Identifiers

HuLuc63-1702

Identifier Type: -

Identifier Source: org_study_id