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

Phase 1

Completed

• Conditions: B-Cell Malignancies
• Interventions: Biological: Urelumab; Biological: Rituximab

• Registration Number: NCT01775631
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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

Detailed Description

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

Study Timeline

• Study First Submitted: 2013-01-23
• Study First Submitted QC: 2013-01-23
• Study First Posted: 2013-01-25
• Study Start: 2013-03
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2016-09
• Last Update Submitted: 2017-03-29
• Last Update Posted: 2017-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm -1 - Urelumab + Rituximab	Urelumab	Urelumab (BMS-663513) flat dose intravenous infusion on specified days Rituximab intravenous flat dose infusion on specified days
Arm -1 - Urelumab + Rituximab	Rituximab	Urelumab (BMS-663513) flat dose intravenous infusion on specified days Rituximab intravenous flat dose infusion on specified days
Arm 1 - Urelumab + Rituximab	Rituximab	Urelumab (BMS-663513) flat dose intravenous infusion on specified days Rituximab intravenous flat dose infusion on specified days
Arm 1 - Urelumab + Rituximab	Urelumab	Urelumab (BMS-663513) flat dose intravenous infusion on specified days Rituximab intravenous flat dose infusion on specified days

Primary Outcome Measures

Name	Time	Method
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	Up to 110 days after last dose of Rituximab

Secondary Outcome Measures

Name	Time	Method
Trough observed serum concentration (Cmin) of Urelumab and Rituximab	12 + 9 time points up to Day 60 of Follow-up
Area under the concentration-time curve (AUC) in one dosing interval (AUC(TAU)) of Urelumab	12 time points up to Day 60 of Follow-up
Maximum observed serum concentration (Cmax) of Urelumab and Rituximab	12 time points up to Day 60 of Follow-up
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	Up to approximately 3 years
Time of maximum observed serum concentration (Tmax) of Urelumab	12 time points up to Day 60 of Follow-up
Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of Urelumab	12 time points up to Day 60 of Follow-up
Immunogenicity of Urelumab in combination with Rituximab as determined by blood sample measurements of anti-drug antibodies (ADA)	Up to approximately 110 days post study drug

Trial Locations

Locations (15)

Ucla Department Of Medicine; 🇺🇸 Los Angeles, California, United States

John Theurer Cancer Center; 🇺🇸 Hackensack, New Jersey, United States

The University Of Texas Md Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Providence Cancer Center Oncology And Hematology Care- Eastside; 🇺🇸 Portland, Oregon, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University Of Iowa Hospitals And Clinics; 🇺🇸 Iowa City, Iowa, United States

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Hospital Of The University Of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University Of Virginia School Of Medicine; 🇺🇸 Charlottesville, Virginia, United States

Dana Faber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami Beach, Florida, United States

University Of Miami Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University Of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States