Combination Study of Urelumab and Rituximab in Patients With B-cell Non-Hodgkins Lymphoma or CLL

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01775631
First received: January 23, 2013
Last updated: August 11, 2014
Last verified: February 2014
  Purpose

The purpose of the study is to determine the safety, tolerability and maximum tolerated dose of Urelumab in combination with Rituximab in patients with B-cell Non-Hodgkins Lymphoma or Chronic Lymphocytic Leukemia (CLL)


Condition Intervention Phase
B-Cell Malignancies
Biological: Urelumab
Biological: Rituxan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-label, Multicenter Study of Urelumab (BMS-663513) in Combination With Rituximab in Subjects With Relapsed/Refractory B-cell Malignancies

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety and tolerability of Urelumab in combination with Rituximab as measured by incidence of adverse events (AEs), serious AEs, death, vital sign changes, electrocardiograms (ECGs), physical examination results, and laboratory test abnormalities [ Time Frame: Up to 60 days after last dose of Urelumab ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Urelumab in combination with Rituximab as measured by incidence of adverse events (AEs), serious AEs, death, vital sign changes, electrocardiograms (ECGs), physical examination results, and laboratory test abnormalities [ Time Frame: Up to 110 days after last dose of Rituximab ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy-Antitumor Activity of Urelumab in combination with Rituximab as measured by best overall response, progression-free survival, time to response, and duration of response [ Time Frame: Up to approximately 2 years ] [ Designated as safety issue: No ]
  • Maximum observed serum concentration (Cmax) of Urelumab and Rituximab [ Time Frame: 15 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of Urelumab [ Time Frame: 15 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of Urelumab [ Time Frame: 15 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Trough observed serum concentration (Cmin) of Urelumab and Rituximab [ Time Frame: 15 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of Urelumab [ Time Frame: 15 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Immunogenicity of Urelumab in combination with Rituximab as determined by blood sample measurements of anti-drug antibodies (ADA) [ Time Frame: Up to approximately 2.33 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 138
Study Start Date: March 2013
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - Urelumab (0.1 mg/kg) + Rituxan (375 mg/m2)

Urelumab (BMS-663513) 0.1 mg/kg intravenous infusion every 3 weeks up to 2 years, depending on response and tolerability to study drug.

Rituxan (Rituximab) 375 mg/m2 intravenous infusion 4 weekly doses every 12 weeks up to 2 years, depending on response and tolerability to study drug

Biological: Urelumab
Other Name: BMS-663513
Biological: Rituxan
Other Name: Rituximab
Experimental: Arm 2 - Urelumab (0.3 mg/kg) + Rituxan (375 mg/m2)

Urelumab (BMS-663513) 0.3 mg/kg intravenous infusion every 3 weeks up to 2 years, depending on response and tolerability to study drug.

Rituxan (Rituximab) 375 mg/m2 intravenous infusion 4 weekly doses every 12 weeks up to 2 years, depending on response and tolerability to study drug

Biological: Urelumab
Other Name: BMS-663513
Biological: Rituxan
Other Name: Rituximab

Detailed Description:

Intervention model: Dose Escalation (part 1) of study= Sequential Design; Dose Expansion (part 2) of study= Parallel Design

  Eligibility

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

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Clinical diagnosis of relapsed/refractory B-cell Malignancies per International Workshop Group (IWG) 2007 criteria or 2008 International Workshop on CLL (IWCLL) criteria
  • Progressed or refractory to at least 1 prior line of standard therapy
  • Subjects in Expansion cohorts are restricted to relapsed/refractory Chronic Lymphocytic Leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) or Follicular Lymphoma (FL) subjects who are refractory to rituximab. Rituximab refractoriness is defined as progression during treatment on prior rituximab therapy or rituximab containing regimen or progression within 6 months from last received dose of rituximab
  • Follicular Lymphoma (FL) must have at least 1 lesion that can be biopsied at screening and on treatment
  • Eastern Cooperative Oncology Group (ECOG) of 0 to 1

Exclusion Criteria:

  • Active or progressing brain metastases
  • Other concomitant malignancies (with some exceptions per protocol)
  • Active or history of autoimmune disease
  • Positive test for human immunodeficiency virus (HIV) 1&2 or known Acquired immune deficiency syndrome (AIDS)
  • History of any hepatitis (A, B or C)
  • History of grade 3-4 drug-related hepatitis
  • Known current drug or alcohol abuse
  • Active tuberculosis (TB)
  • Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-CD137, Anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) or Anti-Glucocorticoid-induced tumor necrosis factor receptor (anti-GITR). However, Anti-Programmed Death-1 (anti-PD-1), Anti-Programmed Death-Ligand1 (anti-PD-L1) are permissible as prior therapy.
  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: NCT01775631

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, California
Ucla Recruiting
Los Angeles, California, United States, 90095
Contact: John Timmerman, Site 0011         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Ronald Levy, Site 0001         
United States, Florida
University Of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Izidore Lossos, Site 0012         
United States, Illinois
Local Institution Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Site 0021         
United States, Iowa
University Of Iowa Hospitals And Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Brian Link, Site 0004         
United States, Massachusetts
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Site 0020         
United States, Michigan
University Of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mark Kaminski, Site 0006         
Local Institution Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Site 0023         
United States, New Jersey
John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, Site 0015         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 11065
Contact: Andrew Zelenetz, Site 0010         
United States, North Carolina
Local Institution Not yet recruiting
Charlotte, North Carolina, United States, 28204
Contact: Site 0022         
United States, Ohio
Local Institution Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Site 0017         
United States, Oregon
Portland Providence Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: John Godwin, Site 0002         
United States, Pennsylvania
Local Institution Not yet recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Site 0019         
United States, Texas
The University Of Texas Md Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sattva Neelapu, Site 0018         
United States, Virginia
Local Institution Not yet recruiting
Charlottesvillle, Virginia, United States, 22908
Contact: Site 0009         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01775631     History of Changes
Other Study ID Numbers: CA186-017
Study First Received: January 23, 2013
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014