Nivolumab for Relapsed or Resistant Blood Cancers

Overseen By Andrew Cowan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Active hepatitis, HIV, Uncontrolled infection, 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: Unknown

Duration: 28 days per cycle

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well nivolumab works for the treatment of hematological malignancies that have come back (relapsed), does not respond (refractory), or is detectable after CAR T cell therapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use other anticancer agents or experimental treatments while participating, and you should not be on systemic corticosteroids or immunosuppressive medications within 14 days of starting the study drug.

Is Nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, has been associated with some serious side effects, including hematological toxicities (blood-related issues) and immune-related adverse events. There have also been reports of hepatitis B reactivation in patients treated with Nivolumab, which can lead to treatment delays or discontinuation. However, it has shown improved tolerability compared to some standard chemotherapy treatments in certain cancers. ^{1 2 3 4 5}

How is the drug Nivolumab unique for treating relapsed or resistant blood cancers?

Nivolumab is unique because it is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, and it is used when other treatments have failed or are not suitable. This approach is different from traditional chemotherapy, which directly targets and kills cancer cells. ^{6 7 8 9 10}

Research Team

Andrew Cowan, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with certain blood cancers like Non-Hodgkin's lymphoma and Chronic lymphocytic leukemia that have returned or didn't respond after CAR T-cell therapy. Participants must not be pregnant, agree to use contraception, and should not have HIV, active infections, or require immunosuppressive drugs.

Inclusion Criteria

My cancer returned or didn't respond after CAR T-cell therapy.

I have been diagnosed with Non-Hodgkin lymphoma or Chronic lymphocytic leukemia.

I am over 18 and can understand and agree to the study's details.

Exclusion Criteria

I am HIV positive.

I am being treated for GVHD, but it's only on my skin and managed with creams.

I have received treatment after my CAR T-cell therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab intravenously over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants are followed up for overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Nivolumab

Trial Overview The study tests Nivolumab in patients whose hematologic malignancies relapsed or are detectable post CAR T-cell treatment. It's a phase II trial to see if this monoclonal antibody can help the immune system fight cancer by stopping tumor growth.

Participant Groups

Group I: Treatment (nivolumab) Experimental Treatment 1 Intervention

Patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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

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]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

Monoclonal antibodies like nivolumab and pembrolizumab, which target PD-1, have shown a survival benefit and better tolerability compared to standard second-line chemotherapy in non-small cell lung cancer, as demonstrated in three phase III trials.

Patients receiving PD-1 inhibitors may experience unique immune-related adverse events that require early recognition and a multidisciplinary management approach, highlighting the need for ongoing education among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. O'Kane, GM., Labbé, C., Doherty, MK., et al.[2018]

In a retrospective study of 26 patients with metastatic renal cell carcinoma treated with nivolumab, all patients experienced some form of adverse event, with fatigue, fever, and anemia being the most common, affecting 27% of patients.

Despite the occurrence of adverse events, including grade 3 reactions in 23% of patients, nivolumab demonstrated favorable safety outcomes in a real-life clinical setting, consistent with findings from other studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. Amores Bermúdez, J., Osman García, I., Unda Urzáiz, M., et al.[2021]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

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]

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 (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 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]

References

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

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

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

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

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. [2018]

4. Spain pubmed.ncbi.nlm.nih.gov

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. 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]

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

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

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]