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

Trial Summary

What is the purpose of this trial?

Background: The drug Nivolumab has been approved to treat some cancers. Researchers want to see if it can slow the growth of other cancers. They want to study its effects on cancers that may have not responded to chemotherapy or other treatments. Objectives: To see if Nivolumab slows the growth of some types of cancer or stops them from getting worse. To test the safety of the drug. Eligibility: People 12 and older who have Epstein-Barr Virus (EBV)-positive lymphoproliferative disorders or EBV-positive non-Hodgkin lymphomas with no standard therapy Design: Participants will be screened with: Medical history Physical exam Blood and urine tests CAT scan of the chest, abdomen, and pelvis Tumor and bone marrow biopsies (sample taken) Magnetic resonance imaging scan of the brain Lumbar puncture (also known as spinal tap) Positron emission tomography/computed tomography scan with a radioactive tracer Every 2 weeks, participants will get Nivolumab by vein over about 1 hour. They will also have: Physical exam Blood and pregnancy tests Review of side effects and medications During the study, participants will repeat most of the screening tests. They may also have other biopsies. After stopping treatment, participants will have a visit every 3 months for 1 year. Then they will have a visit every 6 months for years 2-5, and then once a year. They will have a physical exam and blood tests.

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.

What data supports the effectiveness of the drug Nivolumab for lymphoma?

Nivolumab has shown promising results in treating relapsed or refractory classic Hodgkin lymphoma, with frequent and long-lasting responses. However, its effectiveness in relapsed or refractory follicular lymphoma was limited, with a low response rate and short progression-free survival. ^{1 2 3 4 5}

What safety data exists for Nivolumab (Opdivo) in humans?

Nivolumab, also known as Opdivo, can cause some serious side effects, including blood-related issues, colitis (inflammation of the colon), and myocarditis (inflammation of the heart muscle). These side effects are rare but can be life-threatening, so it's important to monitor for them during treatment. ^{6 7 8 9 10}

How is the drug Nivolumab unique in treating lymphoma?

Nivolumab is unique because it is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, and it has shown promising results in treating relapsed or refractory classic Hodgkin lymphoma, offering an alternative for patients who have not responded to other treatments. ^{1 2 3 5 11}

Research Team

Christopher J Melani, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

I have EBV-positive DLBCL linked to an immune system problem.

My lymphoma is EBV-positive.

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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 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 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]

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]

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]

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, 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

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

Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Fulminant myocarditis induced by immune checkpoint inhibitor nivolumab: a case report and review of the literature. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. [2023]

10. England 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. [2020]

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

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