1875 Participants Needed

Brentuximab Vedotin + Nivolumab for Hodgkin's Lymphoma

Recruiting at 353 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before enrolling, unless they are for specific conditions like adrenal insufficiency or Hodgkin lymphoma symptoms.

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 with other drugs, has been effective in treating relapsed or refractory Hodgkin's lymphoma, with many patients experiencing a good response and longer periods without disease progression. Additionally, Brentuximab Vedotin and Nivolumab have shown activity in patients with relapsed or refractory Hodgkin lymphoma, suggesting potential effectiveness in this combination.12345

What are the safety concerns for Nivolumab in cancer treatment?

Nivolumab, used in cancer treatment, can cause immune-related adverse events (irAEs), which are side effects where the immune system attacks healthy organs. These events can affect the skin, endocrine system, digestive system, respiratory system, and urinary system, with a 26.82% chance of occurring in any grade and a 6.10% chance of being severe. The risk of death from these events is about 0.17%.678910

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

This drug combination is unique because it combines Brentuximab Vedotin, which targets a specific protein on cancer cells, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer, offering a novel approach for patients who have not responded to other treatments.15111213

Research Team

Kara Kelly MD | Roswell Park ...

Kara M. Kelly

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients aged 5-60 with newly diagnosed, untreated classical Hodgkin lymphoma stages I or II. They must have proper kidney and liver function, no severe lung conditions, not be on high-dose steroids or immunosuppressants, and not have other active serious illnesses. Pregnant women and those who haven't agreed to use effective contraception are excluded.

Inclusion Criteria

I am 17 or younger with a moderate ability to carry out daily activities.
ALT =< 3 x ULN
I am between 5 and 60 years old.
See 13 more

Exclusion Criteria

I have a weak immune system that is not well-managed.
Patients with uncontrolled intercurrent illnesses that would jeopardize safety
I haven't taken steroids or immunosuppressants in the last 14 days.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABVD chemotherapy regimen on days 1 and 15 of each 28-day cycle, followed by stratification into different arms based on risk status and response.

8-16 weeks
Multiple visits for chemotherapy administration and imaging

Immunotherapy

Participants in certain arms receive brentuximab vedotin and nivolumab, with or without involved site radiation therapy (ISRT).

8-16 weeks
Regular visits for immunotherapy administration and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for the first year, then every 6 months for the next two years, and annually up to 12 years.

12 years
Regular follow-up visits

Treatment Details

Interventions

  • Brentuximab Vedotin
  • Cyclophosphamide
  • Etoposide
  • Nivolumab
  • Vincristine Sulfate
Trial OverviewThe study compares standard chemotherapy (with drugs like doxorubicin and prednisone) plus radiation against the same treatment combined with immunotherapy drugs Brentuximab Vedotin and Nivolumab. The goal is to see if adding these two drugs improves survival rates.
Participant Groups
8Treatment groups
Experimental Treatment
Active Control
Group I: Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)Experimental Treatment13 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment and imaging, and may undergo blood sample collection as in arm B.
Group II: Arm G (ABVD, eBEACOPP or eBPDac, ISRT)Experimental Treatment18 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment and imaging, and may undergo blood sample collection as in arm C.
Group III: Arm F (ABVD, brentuximab vedotin, nivolumab)Experimental Treatment12 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive treatment as in arm B. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
Group IV: Arm E (ABVD, AVD)Experimental Treatment10 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive AVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, vinblastine IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
Group V: Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)Experimental Treatment13 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive brentuximab vedotin IV and nivolumab IV as in arm B followed by ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
Group VI: Arm C (ABVD, eBEACOPP or eBPDac, ISRT)Experimental Treatment18 Interventions
See Detailed Description.
Group VII: Arm B (ABVD, brentuximab vedotin, nivolumab)Experimental Treatment12 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes once during each treatment cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
Group VIII: Arm A (ABVD)Active Control10 Interventions
Patients are stratified by risk status (favorable versus unfavorable) and then all patients receive the ABVD regimen (doxorubicin hydrochloride IV over 3-15 minutes, bleomycin sulfate IV over at least 10 minutes, vinblastine sulfate IV, and dacarbazine IV over 15-60 minutes) on days 1 and 15 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo FDG-PET/CT or MRI and are identified as RER or SER. Patients then receive ABVD IV for an additional 2 cycles on study. Each cycle lasts 28 days and ABVD is administered on days 1 and 15 of each cycle in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase II trial involving 170 patients with early-stage unfavorable Hodgkin lymphoma, the combination of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) resulted in a higher PET-negative response rate (82.3%) after two cycles compared to the standard ABVD treatment (75.4%).
The 2-year progression-free survival (PFS) rate was also higher in the BV-AVD group (97.3%) compared to the ABVD group (92.6%), indicating that BV-AVD may offer a more effective treatment option for these patients.
Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial.Fornecker, LM., Lazarovici, J., Aurer, I., et al.[2023]
In a study involving 104 patients with advanced classical Hodgkin's lymphoma, both modified eBEACOPP regimens (BrECAPP and BrECADD) achieved high rates of complete response (86% and 88%, respectively) and complete remission, demonstrating their efficacy in treating this condition.
The BrECADD regimen showed a more favorable safety profile with fewer severe organ toxic effects compared to BrECAPP, making it a promising candidate for further testing against standard treatments in future studies.
Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group.Eichenauer, DA., Plütschow, A., Kreissl, S., et al.[2019]
Brentuximab vedotin (Bv) combined with bendamustine (B) showed a high overall response rate of 79% and a complete response rate of 49% in 47 patients with relapsed or refractory classic Hodgkin lymphoma, indicating its efficacy as a treatment option.
The treatment resulted in a median progression-free survival of 18 months and a 2-year overall survival rate of 72%, particularly benefiting patients who achieved a major clinical response and those who underwent stem cell transplantation afterward.
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study.Iannitto, E., Romano, A., Scalzulli, PR., et al.[2021]

References

Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. [2023]
Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group. [2019]
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]
Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. [2022]
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]
Incidence of Infections and Malignancy Among Elderly Male Patients with IBD Exposed to Vedolizumab, Prednisone, and 5-ASA Medications: A Nationwide Retrospective Cohort Study. [2021]
Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. [2022]
Role-Specific Curricular Needs for Identification and Management of Immune-Related Adverse Events. [2023]
Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. [2021]
Association of antibiotic treatment with immune-related adverse events in patients with cancer receiving immunotherapy. [2022]
Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study. [2023]
13.United Statespubmed.ncbi.nlm.nih.gov
Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. [2023]