A Phase 1b/2, Dose-Escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Relapsed Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00742560
First received: August 25, 2008
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

A Phase 1b/2, Multicenter, Open-label, Dose-escalation Study of Elotuzumab (Humanized Anti CS1 Monoclonal IgG1 Antibody) in Combination with Lenalidomide and Dexamethasone in Subjects with Relapsed Multiple Myeloma.


Condition Intervention Phase
Hematologic Cancer
Biological: elotuzumab (HuLuc63)
Drug: lenalidomide
Drug: dexamethasone
Phase 2

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 1b/2, Multicenter, Open-label, Dose-escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Phase 1 Portion: Maximum tolerated dose [ Time Frame: Durng first 4 weeks of elotuzumab dosing ] [ Designated as safety issue: Yes ]
  • Phase 2 portion: Objective response according to the International Myeloma Working group Uniform Response Criteria [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety profile of elotuzumab [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profile of elotuzumab [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: No ]
  • Immunogenicity of elotuzumab [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: No ]
  • Anti tumor activity of elotuzumab [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: No ]
  • Phase 1 portion: Objective response according to the International Myeloma Working group Uniform Response Criteria [ Time Frame: From screening through 60-day follow up period ] [ Designated as safety issue: No ]

Estimated Enrollment: 102
Study Start Date: August 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: elotuzumab, lenalidomide and dexamethasone Biological: elotuzumab (HuLuc63)
Humanized Anti-CS1 Monoclonal IgG1 Antibody
Drug: lenalidomide
25 mg PO days 1 though 21 of each 28 day cycle
Drug: dexamethasone
40 mg PO days 1, 8, 15 and 22 of each 28 day cycle.
Experimental: elotuzumab (lower dosage), lenalidomide and dexamethasone
In the phase 2 portion, patients are randomized to arm 1 or arm 2.
Biological: elotuzumab (HuLuc63)
Humanized Anti-CS1 Monoclonal IgG1 Antibody
Drug: lenalidomide
25 mg PO days 1 though 21 of each 28 day cycle
Drug: dexamethasone
40 mg PO days 1, 8, 15 and 22 of each 28 day cycle.
Experimental: elotuzumab (higher dosage), lenalidomide and dexamethasone
In the phase 2 portion, patients are randomized to arm 1 or arm 2.
Biological: elotuzumab (HuLuc63)
Humanized Anti-CS1 Monoclonal IgG1 Antibody
Drug: lenalidomide
25 mg PO days 1 though 21 of each 28 day cycle
Drug: dexamethasone
40 mg PO days 1, 8, 15 and 22 of each 28 day cycle.

  Eligibility

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

Inclusion Criteria:

  1. Age 18 years or older with a confirmed diagnosis of MM and documentation of one to three prior therapies.
  2. Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior treatment.
  3. Measurable disease M protein component in serum (at least 0.5 g/dL) and/or urine (if present), (>=0.2 g excreted in a 24 hour collection sample). Subjects with free light chain only disease are excluded.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
  5. Creatinine clearance >=50 mL/min measured by Cockcroft-Gault method.
  6. Hematologic parameters defined by:

    • Absolute neutrophil count >1000 cells/mm^3 without growth factors for 7 days.
    • Platelets >=75,000 cells/mm^3 (75 × 10^9/L), without platelet transfusion, within 72 hours of screening evaluation.
    • Hemoglobin >=8 g/dL without red blood cell transfusion within 72 hours of screening.
  7. Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) <3 × upper limit of normal.
  8. Total bilirubin <2 × upper limit of normal, direct bilirubin <2.0 mg/dL.
  9. Negative urine pregnancy test in women of childbearing potential at screening and prior to prescribing lenalidomide. Females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin acceptable methods of birth control for 28 days prior to prescribing lenalidomide. Men must agree to use a latex condom during sexual contact with FCBP even if they have had a successful vasectomy, and must agree not to donate semen during study drug therapy and for a period of time after therapy.
  10. Able 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's privacy regulations).
  11. Able to take aspirin daily as prophylactic anticoagulation therapy (subjects intolerant to aspirin may use warfarin or low-molecular-weight heparin).

Exclusion Criteria:

  1. 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.
  2. Active or prior plasma cell leukemia (defined as either 20% of peripheral WBC comprised of plasma/CD138+ cells or an absolute count of 2 x 10^9/L).
  3. Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure.
  4. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia. 5. Treatment with any investigational drug within 2 weeks or 3 half lives (whichever is longer) of the first dose of elotuzumab.

6. Use of corticosteroids, thalidomide, bortezomib, or cytotoxic chemotherapy within 2 weeks of the first dose of elotuzumab except for steroids with little or no systemic absorption (ie, topical or inhaled steroids).

7. Prior lenalidomide therapy. 8. Prior peripheral stem-cell transplant within 12 weeks of the first dose of elotuzumab.

9. Treatment with nitrosoureas, such as carmustine (BiCNU), nitrogen mustard agents, or melphalan, within 6 weeks of first dose of elotuzumab.

10. Neuropathy >=Grade 3 or painful neuropathy >=Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v3.0). 11. Known active infections requiring IV antibiotic, antiviral, or antifungal therapy. 12. Hypersensitivity to recombinant proteins or excipients in elotuzumab, lenalidomide, or dexamethasone.

13. Female subjects who are pregnant or breastfeeding. 14. Subjects with serum calcium (corrected for albumin) >= 12 mg/dL.

  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: NCT00742560

Locations
United States, Georgia
Site Reference ID/Investigator# 63587
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Site Reference ID/Investigator# 63588
Boston, Massachusetts, United States, 02115
Site Reference ID/Investigator# 63591
Boston, Massachusetts, United States, 02114
United States, Michigan
Site Reference ID/Investigator# 63586
Ann Arbor, Michigan, United States, 48109
Site Reference ID/Investigator# 63592
Detroit, Michigan, United States, 48201
United States, Missouri
Site Reference ID/Investigator# 63589
St. Louis, Missouri, United States, 63110
United States, New York
Site Reference ID/Investigator# 63585
New York, New York, United States, 10029
Canada
Site Reference ID/Investigator# 63582
Calgary, Canada, T2N 2T9
Site Reference ID/Investigator# 63584
Halifax, Canada, B3H 2Y9
Site Reference ID/Investigator# 63583
Toronto, Canada, M5G 2M9
France
Site Reference ID/Investigator# 63562
Lille Cedex, France, 59037
Site Reference ID/Investigator# 63564
Lyon Cedex 08, France, 69373
Site Reference ID/Investigator# 63567
Montpellier Cedex 5, France, 34295
Site Reference ID/Investigator# 63565
Nantes, France, 44000
Site Reference ID/Investigator# 63502
Tours Cedex, France, 37044
Germany
Site Reference ID/Investigator# 63570
Heidelberg, Germany, 69120
Site Reference ID/Investigator# 63569
Kiel, Germany, 24105
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Bristol-Myers Squibb
Investigators
Study Director: Louie Naumovski, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00742560     History of Changes
Other Study ID Numbers: HuLuc63-1703, 2007-006677-83
Study First Received: August 25, 2008
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Paul-Ehrlich-Institut
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by AbbVie:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
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
Neoplasms by Site
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
BB 1101
Antibodies
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014