Nivolumab With DA-REPOCH Chemotherapy Regimen in Treating Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma
A Phase II Study of Nivolumab in Combination With DA-REPOCH Followed by Short Course Nivolumab Consolidation in Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma
2 other identifiers
interventional
30
1 country
1
Brief Summary
This phase II trial studies how well nivolumab works with the DA-REPOCH chemotherapy regimen in treating patients with aggressive B-cell non-Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as dose-adjusted rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (DA-REPOCH), 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 with DA-REPOCH may work better in treating patients with aggressive B-cell non-Hodgkin lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2019
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 19, 2018
CompletedFirst Posted
Study publicly available on registry
November 21, 2018
CompletedStudy Start
First participant enrolled
January 2, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
ExpectedFebruary 6, 2026
February 1, 2026
7.1 years
November 19, 2018
February 4, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
Will be estimated by the method of Kaplan-Meier and the estimate will be provided with 95% confidence intervals. Depending on the number of events, Cox regression model may be used to explore the association between baseline clinical variables and PFS in a univariable manner.
From start of treatment to progression or death, whichever occurs first, assessed at 2 years
Secondary Outcomes (3)
Objective response rate
Up to 8 years
Duration of response defined for all patients who have achieved an objective response (CR or PR)
From date of which patient?s response is documented to the date of progression or death, censoring event-free patients at the time of last follow-up, assessed up to 8 years
Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Up to 30 days post-treatment
Other Outcomes (3)
Major histocompatibility complex (MCH) class I and II expression
Up to 8 years
Expression of PD-1 and PD-L1 with PFS
Up to 8 years
Somatic mutations detection by circulating tumor (ct)-deoxyribonucleic acid (DNA) over time
Up to 8 years
Study Arms (1)
Treatment (nivolumab, DA-REPOCH)
EXPERIMENTALPatients receive rituximab IV and nivolumab IV over 60 minutes on day 1. Patients also receive etoposide, vincristine sulfate and doxorubicin hydrochloride IV continuously over 96 hours, cyclophosphamide IV bolus, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After course 6, patients receive nivolumab IV over 60 minutes on day 1 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given PO
Given IV
Give IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Be willing and able to provide written informed consent/assent for the trial.
- Measurable disease (defined as \>= 1.5 cm in diameter) or at least one PET avid area of disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Absolute neutrophil count (ANC) \>= 1,000 /mcL (within 16 days of treatment initiation).
- Platelets \>= 75,000 / mcL in the absence of transfusion support within 7 days of determining eligibility (within 16 days of treatment initiation).
- Hemoglobin \>= 8 g/dL (within 16 days of treatment initiation).
- Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 40 mL/min creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) (within 16 days of treatment initiation).
- Creatinine clearance should be calculated per institutional standard.
- Serum total bilirubin =\< 1.5 X ULN OR except subjects with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL (within 16 days of treatment initiation).
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 X ULN (within 16 days of treatment initiation).
- Female subject of childbearing potential should have a negative serum pregnancy at screening.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months following the last dose of nivolumab. Subjects should agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months following the last dose of nivolumab. Males must refrain from donating sperm during study participation and for 7 months after the last dose of nivolumab.
- Revised Ann Arbor stage II-IV disease
- Stage I primary mediastinal B-cell lymphoma or mediastinal B cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin?s lymphoma will also be eligible.
- +1 more criteria
You may not qualify if:
- Known hypersensitivity to any of the study drugs.
- History of other malignancy that could affect compliance with the protocol or interpretation of the results.
- Has a diagnosis of immunodeficiency excluding human immunodeficiency virus (HIV) infection or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Subjects may use topical or inhaled corticosteroids or low-dose steroids (=\< 10 mg of prednisone or equivalent per day) as therapy for comorbid conditions. During study participation, subjects may receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions.
- Has a known history of active TB (Bacillus tuberculosis).
- Prior systemic chemotherapy for lymphoma with the exception of corticosteroids for palliation of symptoms and patients with prior indolent non-Hodgkin lymphoma (NHL) treated with single agent rituximab.
- Has known active central nervous system (CNS) lymphoma.
- Richter?s transformation from chronic lymphocytic leukemia (CLL).
- Major surgery within 3 weeks prior to start of study treatment.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Conditions expected to not recur in the absence of an external trigger.
- Has an active infection requiring intravenous systemic therapy or uncontrolled systemic infection including viral, bacterial, or fungal.
- Is unable to swallow capsules or malabsorption syndrome, disease or condition significantly affecting gastrointestinal function.
- Clinically significant cardiovascular disease, including uncontrolled arrhythmia, New York Association class 2- 4 congestive heart failure, or history of myocardial infarction within 6 months.
- Known contraindication to any medication in the treatment plan, including clinically significant peripheral neuropathy.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Female patients who are not surgically sterile or postmenopausal (for at least 1 year) must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 5 months after study treatment:
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- David Bond, MDlead
- Bristol-Myers Squibbcollaborator
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David A Bond, MD
Ohio State University Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
November 19, 2018
First Posted
November 21, 2018
Study Start
January 2, 2019
Primary Completion
February 2, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
February 6, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share