Nivolumab and Combination Chemotherapy in Treating Participants With Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03704714|
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : December 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Aggressive Non-Hodgkin Lymphoma B-Cell Non-Hodgkin Lymphoma CD20 Positive Diffuse Large B-Cell Lymphoma Unclassifiable Intravascular Large B-Cell Lymphoma Primary Mediastinal (Thymic) Large B-Cell Lymphoma T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma||Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Biological: Nivolumab Drug: Prednisone Other: Quality-of-Life Assessment Biological: Rituximab Drug: Vincristine Sulfate||Phase 1 Phase 2|
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)
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.
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 (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study to Evaluate the Safety and Efficacy of Nivolumab in Combination With R-CHOP in a Cohort of Patients With DLBCL/tFL/ High Grade B-NHL|
|Actual Study Start Date :||November 20, 2018|
|Estimated Primary Completion Date :||May 11, 2021|
|Estimated Study Completion Date :||June 11, 2022|
Experimental: Treatment (nivolumab and R-CHOP)
Participants receive nivolumab IV over 30 minutes on day 1. Participants also 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 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.
Drug: Doxorubicin Hydrochloride
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Drug: Vincristine Sulfate
- Maximum tolerated dose (MTD) for the combination treatment of nivolumab and R-CHOP [ Time Frame: Up to 18 months ]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.
- Progression Free Survival (PFS) [ Time Frame: At 18 months ]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.
- Overall response rate (ORR) [ Time Frame: Up to 18 months ]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.
- Overall survival (OS) rate [ Time Frame: At 18 months ]OS rate at 18 months: OS will be measured from the date of enrollment to the date of death from any cause.
- Event-free survival (EFS) [ Time Frame: At 18 months ]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.
- Overall response rates as defined by the RECIL and LYRIC criteria [ Time Frame: Up to 18 months ]RECIL and LYRIC criteria will be evaluated using scans at baseline.
- Frailty/Geriatric Assessments [ Time Frame: Up to 18 months ]Frailty will be assessed using the Geriatric Assessment Tool as developed by the Cancer and Aging Group and the Fried Frailty Index.
- Incidence of Adverse Events [ Time Frame: Up to 42 days after treatment discontinuation ]Toxicity Assessment: Toxicity will be graded using the CTCAE v5.0 and the pro- CTCAE (patient reported symptoms).
- Quality of life Assessment [ Time Frame: Up to 18 months ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03704714
|Contact: Study Coordinator||(312)email@example.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Reem Karmali, MD 312-695-0990|
|Principal Investigator: Reem Karmali, MD|
|Rush University Medical Center||Not yet recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Parameswaran Venugopal 312-942-5978 Parameswaran_Venugopal@rush.edu|
|Principal Investigator: Parameswaran Venugopal|
|Northwestern University- Lake Forest Hospital||Recruiting|
|Lake Forest, Illinois, United States, 60045|
|Contact: Valerie Nelson, MD 847-582-2134|
|Principal Investigator: Valerie Nelson, MD|
|Principal Investigator:||Reem Karmali, MD||Northwestern University|