Brentuximab Vedotin + Nivolumab for Hodgkin's Lymphoma

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Autoimmune disease, CNS involvement, Hepatitis, 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

Compensation: Varies

Number of Visits: 17

Duration: 48 weeks

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of brentuximab vedotin and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory) that have been previously treated with brentuximab vedotin or checkpoint inhibitors. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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. Giving brentuximab vedotin and nivolumab in combination may be an effective treatment in patients with relapsed or refractory classic Hodgkin lymphoma previously treated with brentuximab vedotin or checkpoint inhibitors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.

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

Research shows that Brentuximab Vedotin, when used alone or in combination with other drugs, has been effective in treating Hodgkin's Lymphoma, especially in patients who have relapsed or not responded to previous treatments. It has shown high response rates and prolonged survival in various trials, making it a promising option for managing this condition. ^{1 2 3 4 5}

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

Brentuximab Vedotin is generally well tolerated, with common side effects like peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count). Nivolumab, an anti-PD1 immunotherapy, can cause varied immune-related side effects, such as skin rash and lung issues, but these are manageable with proper care. ^{4 5 6 7 8}

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

This drug combination is unique because it combines Brentuximab Vedotin, an antibody-drug that targets a specific protein on cancer cells, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer. This approach is particularly useful for patients who have not responded to other treatments or are not suitable for standard chemotherapy. ^{1 3 9 10 11}

Research Team

Kristie Blum, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for patients aged 12 or older with classic Hodgkin lymphoma that has relapsed or is refractory after treatment with brentuximab vedotin or checkpoint inhibitors. Participants must have measurable disease, acceptable organ function, and no prior transplants. HIV-positive patients can join if well-managed. Women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

I am 12 years old or older.

Patients with human immunodeficiency virus (HIV) infection are eligible

I am over 18 and can care for myself, or I am 12-18 with moderate activity levels.

Exclusion Criteria

I don't have any infections or serious health issues that would stop me from following the study's requirements.

I do not have hepatitis B or C.

My lymphoma has spread to 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 on day 1 of each 21-day cycle, for up to 16 cycles

48 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

1 visit at 30 days post-treatment, then every 3 months for 2 years, and every 6 months for 3 years

Treatment Details

Interventions

• Brentuximab Vedotin
• Nivolumab

Trial Overview The phase II trial tests the combination of brentuximab vedotin (an antibody-drug conjugate) and nivolumab (a monoclonal antibody immunotherapy) in treating relapsed/refractory classic Hodgkin lymphoma previously treated with either agent but not both. The study aims to see how effective this combo is in such cases.

Participant Groups

Group I: Treatment (brentuximab vedotin, nivolumab) Experimental Treatment 5 Interventions

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 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 1334 patients with untreated stage III or IV Hodgkin's lymphoma, those treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) showed a significant overall survival advantage compared to those receiving the standard ABVD regimen, with a 6-year survival rate of 93.9% versus 89.4%.

A+AVD also resulted in longer progression-free survival and fewer patients requiring subsequent therapies, although it was associated with a higher incidence of peripheral neuropathy, which mostly resolved by the last follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. Ansell, SM., Radford, J., Connors, JM., et al.[2022]

In a phase 3 trial with 1334 patients, brentuximab vedotin combined with chemotherapy (A+AVD) showed a 4.9% higher 2-year modified progression-free survival rate (82.1%) compared to the standard ABVD treatment (77.2%), indicating superior efficacy for advanced-stage Hodgkin's lymphoma.

While A+AVD had a higher incidence of peripheral neuropathy (67% vs. 43% in ABVD), most patients in the A+AVD group experienced resolution or improvement of symptoms, and the treatment was associated with lower rates of severe pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. Connors, JM., Jurczak, W., Straus, DJ., et al.[2023]

Brentuximab vedotin demonstrated a high overall objective response rate of 75% in 102 patients with relapsed Hodgkin lymphoma and 86% in 58 patients with relapsed systemic anaplastic large cell lymphoma, indicating its efficacy as a targeted treatment.

The treatment was generally well tolerated, with peripheral neuropathy being the most common side effect; however, about half of the patients who experienced this side effect saw complete resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Garnock-Jones, KP.[2021]

Brentuximab vedotin is an effective treatment for relapsed or refractory classical Hodgkin lymphoma, showing high response rates and durable outcomes in both clinical trials and real-world settings.

In the phase 3 AETHERA trial, brentuximab vedotin significantly prolonged progression-free survival compared to placebo after autologous stem cell transplant, reducing the risk of disease progression or death by 43% over a median follow-up of 30 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Scott, LJ.[2020]

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]

Brentuximab vedotin, an antibody-drug conjugate used for treating certain lymphomas, showed improved progression-free survival in patients with cutaneous T-cell lymphoma (CTCL) without a direct correlation to the drug's exposure levels, indicating its efficacy is consistent across different exposure ranges.

The study found that while higher exposure to the drug was linked to an increase in severe treatment-emergent adverse events (TEAEs), the results support the use of a standard dose of 1.8 mg/kg every 3 weeks, with the option for dose reductions in patients experiencing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. Suri, A., Mould, DR., Liu, Y., et al.[2019]

Brentuximab vedotin is an effective treatment for relapsed or refractory Hodgkin lymphoma, showing a manageable safety profile with common side effects like peripheral neuropathy and neutropenia.

The drug is contraindicated with bleomycin due to the risk of pulmonary toxicity, and ongoing trials will help clarify its role in frontline therapy and its potential to replace radiation in early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma. Oak, E., Bartlett, NL.[2019]

In a phase 1 trial involving 7 patients with HIV-associated classical Hodgkin lymphoma, the combination of brentuximab vedotin and AVD was well tolerated at a dose of 1.2 mg/kg, with no dose-limiting toxicities identified and a 100% progression-free survival rate at 25 months.

The study highlighted the importance of avoiding strong CYP3A4 inhibitors during treatment, as one patient who took ritonavir experienced severe adverse events, underscoring the need for careful medication management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. Rubinstein, PG., Moore, PC., Rudek, MA., et al.[2020]

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]

References

1. 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]

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

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. [2022]

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

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. [2023]

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

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. [2021]

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

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. [2020]

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

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

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

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. [2019]

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

A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma. [2019]

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

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. [2020]

10. 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]

11. 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]