Nivolumab + Chemotherapy for Non-Hodgkin's Lymphoma

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David Bond, MD

Must not be taking: Immunosuppressants, Anti-PD-1 agents

Disqualifiers: Active infection, CNS lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new combination of treatments for aggressive B-cell non-Hodgkin lymphoma, a cancer affecting the lymphatic system. It combines nivolumab, an immunotherapy that aids the immune system in fighting cancer, with a chemotherapy regimen called DA-REPOCH. The goal is to determine if this combination more effectively stops cancer growth and spread. Individuals with measurable disease, such as a visible tumor or affected area, might be suitable candidates for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or other immunosuppressive treatments, you may need to stop them at least 7 days before starting the trial, unless they are low-dose or for certain conditions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab, when combined with chemotherapy such as the DA-REPOCH regimen, generally maintains a manageable safety profile. In some studies, about 78% of patients experienced immune-related side effects, like inflammation or rash, most of which were mild. More serious side effects occurred in around 39% of patients, with some requiring additional treatment.

However, other studies of nivolumab with standard chemotherapy have not identified major safety concerns. This suggests that while side effects can occur, they are often manageable.

The DA-REPOCH chemotherapy itself has demonstrated consistent safety, regardless of dose level. Overall, these treatments are usually well-tolerated, but like all medical treatments, they can have side effects. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-Hodgkin's lymphoma?

Researchers are excited about the combination of Nivolumab and the DA-REPOCH chemotherapy regimen for treating Non-Hodgkin's Lymphoma because it introduces a novel mechanism of action. Unlike standard chemotherapy treatments, which primarily target and kill rapidly dividing cells, Nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This approach could potentially enhance the effectiveness of traditional chemotherapy by enabling a more targeted immune response against the cancer. By combining these two strategies, there's hope for improved outcomes and potentially fewer side effects compared to conventional treatments alone.

What evidence suggests that nivolumab with DA-REPOCH chemotherapy could be effective for non-Hodgkin's lymphoma?

This trial will evaluate the combination of nivolumab with the DA-REPOCH chemotherapy regimen for aggressive B-cell non-Hodgkin lymphoma. Studies have shown that adding nivolumab to DA-REPOCH may improve outcomes by enhancing the immune system's ability to fight cancer, potentially leading to better disease control. Previous data indicate that a similar treatment, R-da-EPOCH, resulted in 93% of patients not experiencing cancer progression during the study. Additionally, similar treatments showed a 3-year overall survival rate of 99%, suggesting promising long-term results. These findings support the potential effectiveness of using nivolumab with DA-REPOCH for this type of lymphoma. ^{1 6 7 8 9}

Who Is on the Research Team?

David A Bond, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with aggressive B-cell non-Hodgkin lymphoma who can consent to the study, have measurable or PET avid disease, are in fair health (ECOG 0-2), and have normal organ function. Women of childbearing potential must test negative for pregnancy and use birth control; men must also agree to contraception. Exclusions include known drug hypersensitivity, prior chemotherapy (except certain cases), active CNS lymphoma, major surgery within 3 weeks before treatment, other malignancies affecting compliance or results interpretation.

Inclusion Criteria

Creatinine clearance should be calculated per institutional standard

My kidney function, measured by creatinine or GFR, is within the required range.

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)

Exclusion Criteria

I have hepatitis C with cirrhosis.

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

I am a man and will use effective birth control during and 3 months after the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rituximab and nivolumab IV, along with DA-REPOCH chemotherapy regimen, repeated every 21 days for up to 6 courses

18 weeks

6 visits (in-person)

Nivolumab Consolidation

Participants receive nivolumab IV every 28 days for up to 6 courses

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

1 visit at 30 days post-treatment, then every 3 months for 3 years, and every 6 months for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• DA-REPOCH Chemotherapy Regimen
• Nivolumab

Trial Overview The trial tests how well nivolumab works alongside DA-REPOCH chemotherapy (rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) in treating aggressive B-cell non-Hodgkin lymphoma. Nivolumab is an immunotherapy that may boost the immune system's attack on cancer cells while DA-REPOCH aims to stop cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (nivolumab, DA-REPOCH) Experimental Treatment 7 Interventions

Patients 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.

Who Is Running the Clinical Trial?

David Bond, MD

Lead Sponsor

Trials

4

Recruited

110+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of 65 patients with recurrent or refractory non-Hodgkin's lymphoma, the combination of epratuzumab and rituximab was well tolerated and showed an objective response rate of 47%, with the highest response in follicular lymphoma (64%).

The treatment demonstrated promising efficacy, particularly in patients with lower prognostic index scores, and the median duration of response was 16 months for follicular lymphoma, indicating potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. Strauss, SJ., Morschhauser, F., Rech, J., et al.[2017]

In a study involving 11 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of CD19 CAR-T cells and the anti-PD-1 antibody nivolumab was found to be safe, with no dose-limiting toxicities and manageable side effects like cytokine release syndrome in a minority of patients.

The treatment showed promising efficacy, achieving an objective response rate of 81.81% and a complete response rate of 45.45%, indicating strong anti-lymphoma activity that warrants further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. Cao, Y., Lu, W., Sun, R., et al.[2020]

Nivolumab shows a favorable safety profile and a 65% objective response rate in patients with classical Hodgkin lymphoma, indicating its efficacy as a treatment option.

The study recommends a dosing regimen of 240 mg every 2 weeks, as it provides similar drug exposure to the previously used 3 mg/kg every 2 weeks, while maintaining safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. Wang, X., Ludwig, EA., Passarell, J., et al.[2020]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

In a study of 70 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone), the treatment showed comparable outcomes in terms of time to progression and disease-specific survival when matched against a control group of 140 patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Although R-CEOP demonstrated similar progression-free and disease-specific survival rates, it was associated with a lower overall survival rate (30% vs 49% for R-CHOP), likely due to the higher comorbidities and frailty in the R-CEOP group, indicating that while R-CEOP is a viable alternative for patients who cannot tolerate anthracyclines, it may not be as effective overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. Moccia, AA., Schaff, K., Freeman, C., et al.[2021]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

In a study involving 51 patients with newly diagnosed advanced-stage classic Hodgkin lymphoma, nivolumab followed by a combination therapy (N-AVD) showed an impressive objective response rate of 84%, with 67% of patients achieving complete remission.

The treatment was generally well-tolerated, with 59% of patients experiencing grade 3 to 4 treatment-related adverse events, but most were manageable, and the 9-month modified progression-free survival rate was 92%, indicating strong efficacy and safety for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. Ramchandren, R., Domingo-Domènech, E., Rueda, A., et al.[2021]

In a phase II study involving 121 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), nivolumab showed a low overall response rate of 10% in those who failed autologous hematopoietic cell transplantation (auto-HCT) and 3% in those ineligible for auto-HCT, indicating limited efficacy in this patient population.

Despite the low response rates, nivolumab demonstrated a favorable safety profile, with only 24% of patients experiencing grade 3 or 4 adverse events, primarily neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. Ansell, SM., Minnema, MC., Johnson, P., et al.[2019]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03749018

Study Details | NCT03749018 | Nivolumab With DA- ... 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11993899/

Long‐Term Outcomes and Management Strategies With DA ... The median follow‐up was 36.4 months (95% CI: 30.16–45.31). With only one death, related to lymphoma, the 3‐year OS rate was 99% (95% CI: 0.90–1) ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-02699

Nivolumab with DA-REPOCH Chemotherapy Regimen in ... Giving nivolumab with DA-REPOCH may work better in treating patients with aggressive B-cell non-Hodgkin lymphoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12109800/

Optimally Delivered R-da-EPOCH Versus R-CHOP-21 in ... According to the initially published data, R-da-EPOCH resulted in impressive disease control, with event-free survival (EFS) of 93%, long-term ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03586999?term=NCT00337987%20NCT00632827%20NCT00791947%20NCT00930605%20NCT00970385%20NCT01719835%20NCT02809573%20NCT03023358%20NCT03553537%20NCT03586999%20NCT03952572%20NCT04548700%20NCT04922567%20NCT05458180%20NCT05678933&rank=6&tab=results

Study Results | NCT03586999 | Nivolumab With Standard ... Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845026/

Frontline chemoimmunotherapy with nivolumab and dose ... To assess the safety and preliminary efficacy of frontline CPB+chemotherapy in PTCLs, we conducted a phase 1 trial of nivolumab (Nivo) in combination with DA- ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/99/NCT03586999/Prot_SAP_ICF_000.pdf

Nivolumab with standard of care chemotherapy for the first ... We are not aware of any concerning safety signals that have emerged from these studies; however, there are no trials on clinicaltrials.gov combining checkpoint ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121043937

A Pilot Study Using Nivolumab in Combination with ... Immune related AEs of all grades occurred in 78% (N=14) of pts and 39% (N=7) of pts experienced ≥grade 3 irAEs. 44% (N=8) of pts required ...

9. haematologica.org haematologica.org/article/view/12964/79021

Outcomes of patients with relapsed or refractory primary ... Conclusions: This analysis is the largest review of R/R PMBCL to date and demonstrates unfavorable outcomes for patients with refractory disease ...