Nivolumab for Lymphoma

Overseen By Christopher J Melani, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Solid organ transplant, HIV, Hepatitis B, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug Nivolumab (also known as Opdivo) can slow or stop the growth of certain cancers, specifically Epstein-Barr Virus (EBV)-positive lymphoproliferative disorders and non-Hodgkin lymphomas that have not responded well to other treatments. Researchers aim to determine if Nivolumab is a safe and effective option for these cancers. Suitable participants have EBV-positive cancers and no other standard treatment options available. During the trial, participants will receive Nivolumab every 2-4 weeks and undergo regular health checks and scans. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids (more than 10 mg daily prednisone equivalents) or immunosuppressive medications within 14 days of starting the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Nivolumab is likely to be safe for humans?

Research has shown that Nivolumab is generally well-tolerated by patients with certain types of lymphoma. In a previous study, patients with relapsed or refractory Hodgkin lymphoma—whose cancer returned or did not respond to initial treatments—experienced good safety results with Nivolumab. The study confirmed the treatment's effectiveness and safety, even for those who had undergone a stem cell transplant.

Another study found that when patients' tumors either shrank or disappeared completely after receiving Nivolumab, no major safety concerns arose. This suggests that while some side effects may occur, they are usually manageable.

Overall, Nivolumab has been used safely for other cancers, and current research supports its use without significant safety issues. However, participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Nivolumab is unique because it harnesses the power of the immune system to fight lymphoma by blocking the PD-1 pathway, which cancer cells often exploit to avoid detection. Unlike traditional chemotherapy that broadly attacks fast-growing cells, Nivolumab specifically targets immune checkpoints to unleash a more precise immune response against cancer cells. Researchers are excited about Nivolumab because, in addition to its targeted action, it is administered less frequently—either every two or four weeks—instead of the daily or weekly regimens often required by standard treatments, potentially leading to fewer side effects and improved quality of life for patients.

What evidence suggests that Nivolumab might be an effective treatment for lymphoma?

Research has shown that Nivolumab can effectively treat certain cancers. In one study, 14% of patients experienced complete tumor disappearance, while many others saw tumor reduction. Another study found a 92% survival rate when Nivolumab was combined with chemotherapy for advanced Hodgkin lymphoma. In this trial, participants will receive Nivolumab in one of two dosing regimens: either 3mg/kg every 2 weeks or 480 mg every 4 weeks. These results suggest that Nivolumab might help slow cancer growth or prevent it from worsening, especially in cases where other treatments have failed. ^{1 2 3 6 7}

Who Is on the Research Team?

Christopher J Melani, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for people aged 12 and older with EBV-positive lymphoproliferative disorders or non-Hodgkin lymphomas, who have no standard therapy options left. They should be at least two weeks out from previous treatments, have good organ function, and not be pregnant or breastfeeding. Participants must agree to use effective contraception.

Inclusion Criteria

I have EBV-positive lymphoproliferative disease, untreated or relapsed.

Adult subjects have no weight requirement

Women who are not of childbearing potential do not require contraception

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 14 days.

I have a serious health condition that is not under control.

I have had seizures due to brain involvement in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for medical history, physical exam, and various tests

Treatment

Participants receive Nivolumab intravenously every 2 weeks for up to 2 years

Up to 2 years

Bi-weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 1 year, then every 6 months for years 2-5, and then once a year

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The trial is testing Nivolumab's effectiveness in slowing down the growth of certain cancers linked to Epstein-Barr Virus that may not respond well to other treatments. It involves regular infusions of Nivolumab every two weeks along with frequent health checks and tests.

How Is the Trial Designed?

Group I: Nivolumab (B) Experimental Treatment 1 Intervention

Nivolumab, 480 mg IV every 4 weeks for up to 2 years in subjects with responding disease with clinical benefit if they are tolerating treatment

Group II: Nivolumab (A) Experimental Treatment 1 Intervention

Nivolumab, 3mg/kg IV every 2 weeks for up to 2 years in subjects with responding disease with clinical benefit if they are tolerating treatment (closed effective with activation of Amendment C)

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 trial involving 92 patients with relapsed or refractory follicular lymphoma, nivolumab showed a low objective response rate of only 4%, indicating limited efficacy as a monotherapy for this condition.

The study found that responders had a higher presence of CD3+ T cells in their tumors, suggesting that immune response characteristics may play a role in treatment outcomes, while the safety profile of nivolumab remained consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma. Armand, P., Janssens, A., Gritti, G., et al.[2021]

Nivolumab, an immunotherapy drug, can cause immune-mediated side effects like colitis, which may occur even after treatment has stopped.

Using higher doses of methylprednisolone led to a quicker resolution of symptoms in patients compared to previous cases, potentially reducing the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. Walker, H., Brennan, P., Groome, M., et al.[2023]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

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, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, an immune checkpoint inhibitor for metastatic melanoma, can cause immune-related adverse events (irAEs) such as colitis, which were observed in two patients after treatment.

The development of these irAEs is linked to a Th1 dominant immune response, and serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) may serve as potential biomarkers to monitor and manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. Yoshino, K., Nakayama, T., Ito, A., et al.[2020]

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 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 study of patients with non-small cell lung cancer treated with nivolumab, those who experienced serious adverse events (grade ≥3) had significantly better overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to those without such events.

The findings suggest that while serious adverse events are typically concerning, they may be associated with a more favorable treatment response in patients receiving nivolumab, indicating a complex relationship between adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. Blazek, J., Hosek, P., Hrabcova, K., et al.[2023]

A 56-year-old patient with colon cancer developed severe myocarditis after receiving nivolumab, highlighting the potential for serious cardiovascular side effects from this immunotherapy.

The patient successfully recovered with intensive treatment, including extracorporeal membrane oxygenation and corticosteroids, emphasizing the importance of close monitoring and effective management strategies for patients undergoing nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulminant myocarditis induced by immune checkpoint inhibitor nivolumab: a case report and review of the literature. Wang, F., Liu, Y., Xu, W., et al.[2021]

Citations

1. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/hodgkin-lymphoma-nivolumab-avd-first-line

Nivolumab and AVD the New Standard in Hodgkin ... The 2-year progression-free survival rate of 88% among those in this age group treated with nivolumab–AVD “is probably the best ever reported,” ...

2. opdivo.com opdivo.com/relapsed-or-progressed-chl/clinical-trial-results

Classical Hodgkin Lymphoma (cHL) | Clinical Trial Results OPDIVO · Tumors disappeared completely (complete response). 37 out of 258 people, or 14%, saw tumors disappear completely in response · Tumors shrank (partial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7306298/

A Study of Safety and Efficacy of Nivolumab ... In this retrospective trial subsequent chemotherapy or chemotherapy-anti-PD-1 combination helped to achieve an overall response rate (ORR) of 67%. Other ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39413375/

Nivolumab+AVD in Advanced-Stage Classic Hodgkin's ... Conclusions: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage ...

5. oncology-central.com oncology-central.com/nivolumab-improves-survival-and-reduces-long-term-side-effects-for-advanced-hodgkin-lymphoma-patients-2/

Nivolumab plus chemotherapy yields 92% survival rate for ... Advanced Hodgkin lymphoma patients who received chemotherapy alongside Opdivo (nivolumab) had a 92% survival rate and fewer side effects.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1130634324001557

[Translated article] Real-world effectiveness and safety of ... Nivolumab achieved a very durable response in patients who achieved CR (79 months). Nivolumab in combination with chemotherapy rescued 2 trial patients with a ...

7. ashpublications.org ashpublications.org/bloodadvances/article/7/20/6266/497222/Nivolumab-for-relapsed-refractory-classical

5-year survival from the pivotal phase 2 CheckMate 205 study This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT ...