Nivolumab + Brentuximab Vedotin for Hodgkin's Lymphoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two drugs, nivolumab and brentuximab vedotin, in treating high-risk classical Hodgkin lymphoma that has recurred or resisted other treatments. These drugs are types of immunotherapy, designed to help the immune system combat cancer. The trial targets individuals who have already undergone a stem cell transplant and seek additional options to manage their condition. Suitable participants include those with relapsed or difficult-to-treat Hodgkin lymphoma who have completed a stem cell transplant as part of their treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of nivolumab and brentuximab vedotin is generally well-tolerated by patients. Studies have found that these treatments work well together and maintain manageable safety levels when treating recurring or hard-to-treat Hodgkin's lymphoma.

In one study, patients using this combination experienced some side effects, but most were mild to moderate. Common issues included tiredness and nausea, typical with cancer treatments. Serious side effects were less common.

Patients previously treated with these medications had positive results, suggesting that the combination is safe in this context. While side effects can occur, current evidence indicates promising overall safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Brentuximab Vedotin for treating Hodgkin's Lymphoma because it offers a novel approach compared to existing therapies. Nivolumab is an immune checkpoint inhibitor that works by blocking the PD-1 pathway, potentially allowing the immune system to better recognize and attack cancer cells. Meanwhile, Brentuximab Vedotin is an antibody-drug conjugate that delivers a potent chemotherapy agent directly to the cancer cells, minimizing damage to healthy cells. This dual mechanism could enhance the treatment's effectiveness while potentially reducing some of the side effects associated with traditional chemotherapy.

What evidence suggests that nivolumab and brentuximab vedotin might be effective treatments for Hodgkin's lymphoma?

Research has shown that using nivolumab and brentuximab vedotin together may help treat Hodgkin's lymphoma. In this trial, participants will receive this combination treatment. Studies have found that this combination can greatly improve survival rates for people with classic Hodgkin lymphoma. Nivolumab helps the immune system fight cancer cells, while brentuximab vedotin has proven effective for patients whose disease has returned or hasn't responded to other treatments. Together, these treatments have shown better results in slowing the disease. This evidence suggests that this combination could be very helpful for those with recurring or hard-to-treat Hodgkin's lymphoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Alex Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

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

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

2. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3750/537086/Brentuximab-vedotin-and-nivolumab-for-untreated

Brentuximab vedotin and nivolumab for untreated patients ... Brentuximab vedotin and nivolumab for untreated patients with Hodgkin lymphoma: long-term results Open Access. Clinical Trials & Observations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02572167

NCT02572167 | A Study of Brentuximab Vedotin ... The purpose of this study is to assess the safety profile and antitumor activity of brentuximab vedotin administered in combination with nivolumab in ...

4. nature.com nature.com/articles/s41408-025-01257-1

Outcomes in patients with classic Hodgkin lymphoma ... Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL)

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8619646/

Efficacy and safety of nivolumab combined with ... Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–1566 ...

6. ashpublications.org ashpublications.org/blood/article/138/6/427/475691/Brentuximab-vedotin-in-combination-with-nivolumab

Brentuximab vedotin in combination with nivolumab in ... BV and Nivo with staggered or concurrent dosing were active and well tolerated when used as first salvage therapy in patients with r/r cHL.

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2405888

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