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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nivolumab for treating Non-Hodgkin's Lymphoma?

Nivolumab has shown effectiveness in improving survival and response rates in patients with advanced squamous non-small cell lung cancer after chemotherapy, suggesting it may also be beneficial in other cancers like Non-Hodgkin's Lymphoma. ^{1 2 3 4 5}

Is the combination of Nivolumab and chemotherapy safe for treating non-Hodgkin's lymphoma?

Research shows that combining Nivolumab with other treatments for non-Hodgkin's lymphoma is generally safe, with no severe dose-limiting toxicities reported. Some patients experienced mild to moderate side effects like cytokine release syndrome (a reaction that can cause fever and fatigue) and neurotoxicity (affecting the nervous system), but these were manageable. ^{6 7 8 9 10}

What makes the drug Nivolumab unique for treating Non-Hodgkin's Lymphoma?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, and it has shown benefits in various cancers, including Hodgkin lymphoma. When combined with the DA-REPOCH chemotherapy regimen, it offers a novel approach by potentially enhancing the immune response against Non-Hodgkin's Lymphoma. ^{1 10 11 12 13}

What is the purpose of this trial?

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.

Research Team

David A Bond, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Response to first line chemotherapy regimen is associated with efficacy of nivolumab in non-small-cell lung cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

DA-REPOCH Versus R-CHOP for the Treatment of Activated B-Cell Subtype Diffuse Large B-Cell Lymphoma: A Community Center Experience. [2020]

7. United States 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. [2017]

8. Switzerland 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. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. [2021]

10. United States 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. [2021]

13. New Zealand pubmed.ncbi.nlm.nih.gov

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