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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of nivolumab, a type of immunotherapy, in treating certain blood cancers that have returned or do not respond to other treatments. Nivolumab helps the body’s immune system attack cancer cells, potentially stopping their growth and spread. Individuals with specific types of non-Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma, particularly if their disease is resistant or has returned after CAR T-cell therapy, might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to benefit from a promising therapy.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that nivolumab is generally well-tolerated by patients with various cancers, including blood cancers. Studies have found that the most common side effects include a low white blood cell count and an underactive thyroid, both of which can be managed. Although serious side effects are rare, they remain possible. The FDA has already approved nivolumab for certain types of classical Hodgkin lymphoma, which supports confidence in its safety. While side effects can occur, they usually do not outweigh the potential benefits for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it targets the PD-1 pathway, a mechanism that helps cancer cells evade the immune system. Unlike traditional chemotherapy, which directly kills rapidly dividing cells but can affect healthy cells too, Nivolumab works by boosting the body's own immune response specifically against cancer cells. This immunotherapy approach is potentially less toxic and offers a more targeted attack on blood cancers, which is why researchers are excited about its promise in treating relapsed or resistant cases.

What evidence suggests that nivolumab might be an effective treatment for blood cancers?

Research has shown that nivolumab, the treatment under study in this trial, effectively treats certain blood cancers, particularly when classical Hodgkin's lymphoma returns or resists other treatments. Studies have found that about 84.2% of patients responded well to nivolumab, with 52.6% achieving a complete response, meaning no signs of cancer were found. This treatment aids the immune system in identifying and destroying cancer cells. Some patients have experienced long-lasting benefits, with responses lasting up to 23.1 months. Overall, nivolumab shows promising results for those with hard-to-treat blood cancers. ^{1 4 6 7 8}

Who Is on the Research Team?

Rahul Banerjee, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 (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]

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]

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]

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]

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]

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 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]

Citations

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sciencedirect.com

sciencedirect.com/science/article/pii/S1130634324001557

[Translated article] Real-world effectiveness and safety of ...

Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed favourable effectiveness data in the study sample.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12266480/

Nivolumab for relapsed and refractory classical Hodgkin ...

Immune checkpoint inhibitors, including nivolumab, have demonstrated high therapeutic efficacy in relapsed and refractory HL patients.

3.

opdivo.com

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

Classical Hodgkin Lymphoma (cHL) | Clinical Trial Results

Of the people who responded to OPDIVO, the shortest response lasted less than one month, and the longest response lasted 23.1 months.

4.

emjreviews.com

emjreviews.com/flagship-journal/article/single-agent-low-dose-nivolumab-in-patients-with-relapsed-refractory-hodgkins-lymphoma-as-a-bridge-to-stem-cell-transplant-j190125/

Single-Agent Low-Dose Nivolumab in Patients with ...

Low-dose nivolumab (40 mg every 2 weeks) maintains high efficacy with excellent tolerability and offers dramatic cost savings by three-to-seven- ...

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ashpublications.org

ashpublications.org/blood/article/142/Supplement%201/6175/501325/Evaluation-of-Efficacy-and-Safety-of-Nivolumab-in

Evaluation of Efficacy and Safety of Nivolumab in Treatment of ...

Overall response rate (ORR) was 84.2% includes 52.6% of patients has achieved complete response (CR). In the patients who received the Nivolumab ...

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opdivohcp.com

opdivohcp.com/

OPDIVO® (nivolumab) | Healthcare Professional Website

Find efficacy and safety data, dosing schedules, and resources for both you and your patients. SELECT INDICATION. Non-Small Cell Lung Cancer (NSCLC).

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11196337/

Safety of nivolumab monotherapy in five cancer types

This is the largest study examining the safety of nivolumab-treated patients in real-world clinical practice including rare but potentially serious TRAEs.

8.

opdivo.com

opdivo.com/relapsed-or-progressed-chl

Classical Hodgkin Lymphoma (cHL) Cancer Treatment

OPDIVO® (nivolumab) is a treatment option for certain adults with previously treated classical Hodgkin lymphoma (cHL) whose cancer has come back or spread.