Nivolumab + Brentuximab Vedotin for Hodgkin's Lymphoma

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: CNS involvement, Pneumonitis, Autoimmune, 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: 38

Duration: 24 weeks

62 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 corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study drugs, unless they are inhaled, topical, or low-dose adrenal replacements.

What data supports the effectiveness of the drug combination of Nivolumab and Brentuximab Vedotin for Hodgkin's Lymphoma?

Research shows that the combination of Nivolumab and Brentuximab Vedotin is effective in patients with relapsed or refractory Hodgkin lymphoma, with some patients achieving long-term remission. This combination has shown promise, especially in cases where other treatments have failed. ^{1 2 3 4 5}

Is the combination of Nivolumab and Brentuximab Vedotin safe for humans?

The combination of Nivolumab and Brentuximab Vedotin has been studied in patients with Hodgkin's lymphoma, showing an acceptable safety profile. Common side effects include peripheral neuropathy (nerve damage causing tingling or numbness) from Brentuximab Vedotin and immune-related side effects from Nivolumab, such as skin rash and inflammation of the colon or lungs. ^{1 2 4 6 7}

What makes the drug combination of Nivolumab and Brentuximab Vedotin unique for treating Hodgkin's Lymphoma?

The combination of Nivolumab and Brentuximab Vedotin is unique because it targets the immune system to fight Hodgkin's Lymphoma, especially in patients who are older or cannot tolerate standard chemotherapy. Nivolumab blocks a protein that prevents the immune system from attacking cancer cells, while Brentuximab Vedotin delivers chemotherapy directly to cancer cells, making this combination effective for those who have relapsed or are not responding to other treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This phase II trial studies how well nivolumab and brentuximab vedotin work after stem cell transplant in treating patients with high-risk classical Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and brentuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Research Team

Alex Herrera

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with high-risk classical Hodgkin lymphoma that's returned or isn't responding to treatment. They must have completed a stem cell transplant, be Brentuximab Vedotin naive or responsive, and meet specific health criteria including organ function tests. Women of childbearing potential and men must use effective contraception.

Inclusion Criteria

My diagnosis is classical Hodgkin lymphoma, not the nodular type, confirmed by a specialist.

Documented informed consent

Agreement to allow the use of archival tissue from pre-ASCT tumor biopsies

Exclusion Criteria

I do not have peripheral neuropathy, immunodeficiency, or autoimmune diseases.

I am not pregnant, breastfeeding, or have heart problems.

My lymphoma affects my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin and nivolumab intravenously every 21 days for up to 8 cycles

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Visits at 30 and 100 days, 3, 6, 12, and 18 months, then biannually

Treatment Details

Interventions

• Brentuximab Vedotin
• Nivolumab

Trial Overview The study is testing the effectiveness of Nivolumab and Brentuximab Vedotin after an autologous stem cell transplant (SCT). It aims to see if these immunotherapies can help the immune system fight cancer by preventing tumor growth and spread in patients with recurrent or refractory Hodgkin lymphoma.

Participant Groups

Group I: Treatment (brentuximab vedotin, nivolumab) Experimental Treatment 3 Interventions

Beginning 30-60 days post-ASCT, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles 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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 2 trial involving 46 older patients with untreated Hodgkin lymphoma, the combination of brentuximab vedotin and nivolumab showed an overall response rate of 61%, indicating its potential efficacy in this population, particularly those with comorbidities.

The treatment was generally well tolerated, although 48% of patients experienced peripheral neuropathy, and there were some serious adverse events, including one treatment-related death, suggesting that while the regimen is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Cheson, BD., Bartlett, NL., LaPlant, B., et al.[2020]

In a phase 1/2 trial involving 64 patients with relapsed or refractory Hodgkin lymphoma, the combination of brentuximab vedotin with nivolumab showed a high overall response rate of 89%, indicating strong efficacy in treating this type of cancer.

The study also reported varying levels of treatment-related adverse events, with the triplet therapy group experiencing the highest rate of severe side effects (50%), highlighting the importance of balancing efficacy with safety in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Diefenbach, CS., Hong, F., Ambinder, RF., et al.[2021]

In a study of 21 patients with relapsed and refractory classic Hodgkin lymphoma who had previously failed nivolumab treatment, the combination of nivolumab and brentuximab vedotin showed a promising overall response rate of 57%.

The treatment was found to be relatively safe, with 63% of patients experiencing any grade adverse events, and only 10% experiencing severe (grade 3-4) adverse events, suggesting that this combination therapy could be a viable option for patients after PD-1 inhibitor failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. Fedorova, LV., Lepik, KV., Volkov, NP., et al.[2023]

Brentuximab vedotin, a targeted therapy for Hodgkin lymphoma, is effective for patients at high risk of recurrence or relapse, but it can cause significant side effects, particularly peripheral neuropathy.

For patients who relapse after brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) is an option, though it carries unpredictable immune-related side effects, highlighting the need for careful management in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. Michot, JM., Lazarovici, J.[2023]

In a phase 2 study involving 80 patients with relapsed classical Hodgkin's lymphoma, nivolumab demonstrated a high objective response rate of 66.3%, indicating its efficacy as a treatment option after failure of both autologous stem-cell transplantation and brentuximab vedotin.

Nivolumab was found to have an acceptable safety profile, with common side effects including fatigue and infusion-related reactions, and no treatment-related deaths reported, suggesting it is a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Younes, A., Santoro, A., Shipp, M., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. [2020]

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

Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. [2021]

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

Durable Responses with Brentuximab Vedotin in cHL. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. [2023]

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

Brentuximab vedotin in pretreated Hodgkin lymphoma patients: a systematic review and meta-analysis. [2019]

6. France pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]

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

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. [2022]