Brentuximab Vedotin + Nivolumab for Hodgkin's Lymphoma

Recruiting at 4 trial locations

Overseen By Alex Herrera, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressives, others

Disqualifiers: CNS involvement, Autoimmune disease, 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: 24

Duration: 48 weeks

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates how well brentuximab vedotin and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back after initial treatment (relapsed) or has not responded to initial treatment (refractory). 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. Nivolumab is an antibody that enhances the immune system to better fight Hodgkin lymphoma cells. Giving brentuximab vedotin and nivolumab may be able to defer stem cell transplant treatment and spare the considerable cost and toxicity on transplantation.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain investigational therapies or systemic treatments like high-dose corticosteroids within 14 days of starting the study drugs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination Brentuximab Vedotin and Nivolumab for treating 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 after previous treatments. It has shown high response rates and prolonged survival in various trials, making it a promising option for those with difficult-to-treat cases. ^{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 immune-related side effects that are varied and unpredictable, such as skin rash and lung issues. ^{2 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, which helps the immune system attack cancer cells. This approach is particularly useful for patients who have not responded to other treatments or are not suitable for standard chemotherapy. ^{1 4 9 10 11}

Research Team

Alex F. Herrera

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with classical Hodgkin lymphoma that has returned or didn't respond to first treatment. They must have had only one prior therapy, no severe allergies to the drugs being tested, and no active major diseases like heart problems or uncontrolled infections. Participants need normal organ function tests and agree to use birth control.

Inclusion Criteria

Agreement by women and men of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months (women) or 7 months (men) after the last dose of protocol therapy

I was treated with BV or anti-PD-1/PD-L1, achieved complete remission, and haven't relapsed in 6 months.

I am not eligible for a stem cell transplant due to my age, health conditions, or personal choice.

Exclusion Criteria

You had a severe allergic reaction (grade 3 or higher) to brentuximab vedotin or nivolumab in the past.

I have had progressive multifocal leukoencephalopathy in the past.

My cervical cancer is in its early stages and has not spread.

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 16 cycles

48 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

8 visits (in-person)

Treatment Details

Interventions

• Brentuximab Vedotin
• Nivolumab

Trial Overview The study is testing brentuximab vedotin (an antibody-drug conjugate) combined with nivolumab (a drug boosting the immune system) in patients with relapsed/refractory classical Hodgkin lymphoma. The goal is to see if this combo can delay or replace stem cell transplant treatments.

Participant Groups

Group I: Treatment (brentuximab vedotin, nivolumab) Experimental Treatment 2 Interventions

Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

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?

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 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]

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]

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

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

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

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

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

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

5. 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]

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]