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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01775631
First received: January 23, 2013
Last updated: May 25, 2016
Last verified: January 2016
  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

Condition Intervention Phase
B-Cell Malignancies
Biological: Urelumab
Biological: Rituximab
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 3 years ] [ Designated as safety issue: No ]
  • Maximum observed serum concentration (Cmax) of Urelumab and Rituximab [ Time Frame: 12 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: 12 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: 12 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: 12 + 9 time points up to Day 60 of Follow-up ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve (AUC) in one dosing interval (AUC(TAU)) of Urelumab [ Time Frame: 12 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 110 days post study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 74
Study Start Date: March 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm -1 - Urelumab + Rituximab

Urelumab (BMS-663513) flat dose intravenous infusion on specified days

Rituximab intravenous flat dose infusion on specified days

Biological: Urelumab
Other Name: BMS-663513
Biological: Rituximab
Experimental: Arm 1 - Urelumab + Rituximab

Urelumab (BMS-663513) flat dose intravenous infusion on specified days

Rituximab intravenous flat dose infusion on specified days

Biological: Urelumab
Other Name: BMS-663513
Biological: 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 (B-Non-Hodgkins Lymphoma (NHL)) per International Workshop Group (IWG)
  • Progressed or refractory to at least 1 prior line of standard therapy
  • Subjects in Expansion cohorts are restricted to relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Follicular Lymphoma (FL) subjects who are either relapsed or refractory to prior rituximab or ritxumab-containing chemotherapy regimens
  • 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

Locations
United States, California
Ucla
Los Angeles, California, United States, 90095
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
University Of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
United States, Iowa
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University Of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 11065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Oregon
Portland Providence Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
Hospital Of The University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The University Of Texas Md Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
University Of Virginia School Of Medicine
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
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: May 25, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 26, 2016