This phase I/II trial studies the side effects and best dose of nivolumab and how well it works when giving together with combination chemotherapy in treating participants with diffuse large B-cell lymphoma. Monoclonal antibodies, such as nivolumab, interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and combination chemotherapy may work better in treating participants with diffuse large B-cell lymphoma.
PRIMARY OBJECTIVES: I. To identify the maximum tolerated dose (MTD) for the combination treatment of nivolumab and rituximab, cyclophosphamide, doxorubicin hydrochloride (doxorubicin), vincristine sulfate (vincristine), and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL). (Phase I) II. To assess the impact of nivolumab + R-CHOP on response by looking at complete response (CR) rates. (Phase II) SECONDARY OBJECTIVES: I. To look at preliminary efficacy as measured by overall response rate for combination nivolumab + R-CHOP. II. To assess the impact of nivolumab + R-CHOP on survival outcomes, specifically progression-free survival (PFS), overall survival (OS) and event-free-survival (EFS). III. To assess toxicity and tolerability of patients treated with nivolumab + R-CHOP. IV. To assess quality of life in patients treated with nivolumab + R-CHOP. EXPLORATORY OBJECTIVES: I. To explore the impact of the PD-1:PD-L1 regulatory axis and targeting this axis on the immune microenvironment. II. To identify the process of cachexia as a potential mechanism of resistance to anti-PD-1 therapy. OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study. Participants receive nivolumab intravenously (IV) over 30 minutes on day 1. Participants also receive rituximab IV on day 2, cyclophosphamide IV on day 2, doxorubicin hydrochloride IV over 3-5 hours on day 2, vincristine sulfate IV over 30 minutes on day 2, and prednisone orally (PO) on days 2-6 of course 1 and rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV over 3-5 hours on day 1, vincristine sulfate IV over 30 minutes on day 1, and prednisone PO on days 1-5 of courses 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed for up to 18 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given IV
Given IV
Given IV
Given PO
Ancillary studies
Given IV
Given IV
Northwestern University
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Northwestern University- Lake Forest Hospital
Lake Forest, Illinois, United States
Northwestern Medicine: Delnor, DuPage, Warrenville, Kishwaukee (West Region)
Warrenville, Illinois, United States
Maximum tolerated dose (MTD) for the combination treatment of nivolumab and R-CHOP
To identify the MTD for the combination treatment of nivolumab and R-CHOP in patients with DLBCL, this will be established during Phase I using a modified 3+3 dose escalation.
Time frame: Up to 18 months
Progression Free Survival (PFS)
To assess the impact of nivolumab + R-CHOP on PFS at 18 months: This will be the proportion of patient that will be alive and progression free at 18 months.
Time frame: At 18 months
Overall response rate (ORR)
Will be defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as assessed by the investigators using Lugano criteria.
Time frame: Up to 18 months
Overall survival (OS) rate
OS rate at 18 months: OS will be measured from the date of enrollment to the date of death from any cause.
Time frame: At 18 months
Event-free survival (EFS)
EFS rate at 18 months: EFS will be measured from the date of enrollment to the date of first documented disease progression, relapse, discontinuation of therapy for any reason, initiation of new anti-lymphoma therapy or death from any cause.
Time frame: At 18 months
Overall response rates as defined by the RECIL and LYRIC criteria
RECIL and LYRIC criteria will be evaluated using scans at baseline.
Time frame: Up to 18 months
Frailty/Geriatric Assessments
Frailty will be assessed using the Geriatric Assessment Tool as developed by the Cancer and Aging Group and the Fried Frailty Index.
Time frame: Up to 18 months
Incidence of Adverse Events
Toxicity Assessment: Toxicity will be graded using the CTCAE v5.0 and the pro- CTCAE (patient reported symptoms).
Time frame: Up to 42 days after treatment discontinuation
Quality of life Assessment
Quality of life with treatment will be measured using Patient Reported Outcomes Measurement Information System (PROMIS) based measures and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30).
Time frame: Up to 18 months
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