A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma
Enrollment to this study was discontinued after four subjects due to industry-related changes to the Cabiralizumab program.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Nivolumab is a human monoclonal antibody (HuMAb; immunoglobulin G4 \[IgG4\]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens. Nivolumab will be delivered intravenously at a fixed dose of 240 mg on day 1 of 14 day cycles.
Cabiralizumab is a recombinant, humanized Immunoglobulin G4 (IgG4) monoclonal antibody that binds to human colony stimulating factor 1 receptor (CSF1R; c-fms). Cabiralizumab will be delivered intravenously at a dosage of 4 mg/kg on day 1 of 14 day cycles.
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Unviersity of Wisconsin
Madison, Wisconsin, United States
Overall Response Rate (ORR) at Four Months (LYRIC Criteria)
Overall Response Rate (CR + PR) as determined by LYRIC (LYmphoma Response to Immunomodulatory therapy Criteria), at four months (shown as number of participants with CR or PR at 4 months). LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR). * IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration * IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment. * IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.
Time frame: 4 months
Complete Response Rate (CRR) at Four Months
Complete response rate, as determined by LYRIC criteria, at four months (reported as number of participants with CR at 4 months). LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR). * IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration * IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment. * IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.
Time frame: 4 months
Overall Response at Four Months by (LUGANO 2014) Criteria
Overall response (CR + PR), as determined by LUGANO 2014 criteria (reported as number of participants with a CR or PR at 4 months). The Lugano classification is utilized for both lymphoma staging and response assessment and incorporates PET-CT imaging. Responses are described as either partial or complete, with a complete response requiring disappearance of metabolically active sites of disease.
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Time frame: four months
Complete Response Rate at Four Months (LUGANO 2014) Criteria
Complete Response Rate, as determined by LUGANO 2014 criteria, at (reported as number of participants with a CR at 4 months). The Lugano classification is utilized for both lymphoma staging and response assessment and incorporates PET-CT imaging. A complete response requires disappearance of metabolically active sites of disease.
Time frame: four months
Progression-Free Survival (PFS)
Progression-Free Survival will be measured as number of patients alive at 3, 6, 9 and 12 months.
Time frame: 3, 6, 9 and 12 months post starting study treatment
Disease Control Rate (DCR)
The proportion of all subjects with stable disease (SD) for 8 weeks, PR, or CR.
Time frame: at time of study drug discontinuation, average of 7 months
Duration of Response (DOR)
Duration of Response measured from the time that measurement criteria are met for CR or PR (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).
Time frame: at time of study drug discontinuation, up to 3 years
Time to Next Treatment (TNT)
Time to next treatment (TNT) is defined as the time from the date of enrollment to the institution of next treatment.
Time frame: Up to 1 year post discontinuation of therapy, average of 24 months
Summarize Adverse Events
Assess and summarize adverse events (AEs) using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: From time of consent through 100 days post treatment discontinuation. Longest actual collection for AEs: 13 months. Average of 9.5 Months