Clinical trial NCT01775631: Combination Study of Urelumab and Rituximab in Patients With B-cell Non-Hodgkins Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-Cell Malignancies
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-01-25
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Up to 60 days after last dose of Urelumab
measure: 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
timeFrame: Up to 110 days after last dose of Rituximab
Secondary outcomes:
measure: 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
timeFrame: Up to approximately 3 years
measure: Maximum observed serum concentration (Cmax) of Urelumab and Rituximab
timeFrame: 12 time points up to Day 60 of Follow-up
measure: Time of maximum observed serum concentration (Tmax) of Urelumab
timeFrame: 12 time points up to Day 60 of Follow-up
measure: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of Urelumab
timeFrame: 12 time points up to Day 60 of Follow-up
measure: Trough observed serum concentration (Cmin) of Urelumab and Rituximab
timeFrame: 12 + 9 time points up to Day 60 of Follow-up
measure: Area under the concentration-time curve (AUC) in one dosing interval (AUC(TAU)) of Urelumab
timeFrame: 12 time points up to Day 60 of Follow-up
measure: Immunogenicity of Urelumab in combination with Rituximab as determined by blood sample measurements of anti-drug antibodies (ADA)
timeFrame: Up to approximately 110 days post study drug
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ucla Department Of Medicine
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University Of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Iowa City
country: United States
facility: University Of Iowa Hospitals And Clinics
state: Iowa
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Portland
country: United States
facility: Providence Cancer Center Oncology And Hematology Care- Eastside
state: Oregon
city: Philadelphia
country: United States
facility: Hospital Of The University Of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University Of Virginia School Of Medicine
state: Virginia
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: