B-Cell Malignancies
Conditions
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
Interventions
BIOLOGICALUrelumab
BIOLOGICALRituximab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 60 days after last dose of Urelumab |
Secondary
| Measure | Time frame |
|---|---|
| Maximum observed serum concentration (Cmax) of Urelumab and Rituximab | 12 time points up to Day 60 of Follow-up |
| 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 |
| 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 |
| 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 |
| 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 |
| Trough observed serum concentration (Cmin) of Urelumab and Rituximab | 12 + 9 time points up to Day 60 of Follow-up |
Countries
United States
Outcome results
None listed