146 Participants Needed

Brentuximab Vedotin + Nivolumab ± Ipilimumab for Hodgkin's Lymphoma

Recruiting at 530 trial locations
JE
Tatjana Kolevska, MD profile photo
Overseen ByTatjana Kolevska, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic corticosteroids or other immunosuppressants at least 2 weeks before starting the study treatment. If you are on replacement doses of steroids for adrenal insufficiency, you may continue those. It's best to discuss your specific medications with the study team to ensure compliance with the trial requirements.

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

Research shows that Brentuximab Vedotin, when used with other drugs, has been effective in treating Hodgkin's Lymphoma, with a high response rate in patients who had relapsed after previous treatments. Additionally, combining Brentuximab Vedotin with immune-boosting drugs like Nivolumab and Ipilimumab may enhance its effectiveness by activating the body's immune response against the cancer.12345

What is known about the safety of Brentuximab Vedotin, Nivolumab, and Ipilimumab for Hodgkin's Lymphoma?

Brentuximab Vedotin is generally well tolerated but can cause side effects like peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count). Nivolumab, an anti-PD1 immunotherapy, can have unpredictable immune-related side effects such as skin rash, colitis (inflammation of the colon), and lung issues. Ipilimumab's safety profile is not detailed in the provided research, but it is known to have immune-related side effects similar to Nivolumab.45678

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

This drug combination is unique because it combines targeted chemotherapy with immune-activating drugs to enhance the body's ability to fight Hodgkin's Lymphoma, especially in cases where the disease has returned or not responded to previous treatments.19101112

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. 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. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

Research Team

CS

Catherine S Diefenbach

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Adults with recurrent or refractory classical Hodgkin lymphoma can join this trial. They must have finished previous treatments at least 21 days before, not be pregnant or breastfeeding, and agree to use contraception. Those with serious autoimmune diseases, uncontrolled infections like HIV, severe lung issues, recent monoclonal antibody therapy within 6 months (except ipilimumab in some cases), or a history of certain severe drug reactions are excluded.

Inclusion Criteria

All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
Human immunodeficiency virus (HIV) positive patients are allowed on this study if they have a CD4 count > 400, and are on a stable antiviral regimen; patients with poorly controlled HIV or other chronic active viral infections will be excluded
Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed
See 20 more

Exclusion Criteria

RANDOMIZED PHASE II (ARMS K AND L): Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
RANDOMIZED PHASE II (ARMS K AND L): Patients must have relapsed after first line chemotherapy; may have relapsed after autologous stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; patient must not have received a prior allogeneic stem cell transplant (out of risk of reactivation of pulmonary graft versus host disease [GVHD])
Patients must not have grade 2 or greater peripheral sensory neuropathy
See 34 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive brentuximab vedotin, nivolumab, and ipilimumab in various combinations across different arms. Treatment cycles vary between 21 and 14 days, with up to 46 cycles in total.

Up to 34 months
Regular visits every 14-21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes imaging and blood tests.

10 years
Every 3 months for 1 year, then every 6 months for 2 years, and annually thereafter

Treatment Details

Interventions

  • Brentuximab Vedotin
  • Ipilimumab
  • Nivolumab
Trial Overview The trial is testing the combination of brentuximab vedotin and nivolumab with or without ipilimumab to see how well they work against Hodgkin lymphoma that has come back or hasn't responded to treatment. It's looking for the best dose and side effects while checking if these drugs help the immune system fight cancer more effectively.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Phase II Arm II (brentuximab vedotin, nivolumab, ipilimumab)Experimental Treatment7 Interventions
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Group II: Phase II Arm I (brentuximab vedotin, nivolumab)Experimental Treatment6 Interventions
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Group III: Phase I Arm III (brentuximab vedotin, nivolumab, ipilimumab)Experimental Treatment7 Interventions
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Group IV: Phase I Arm II (brentuximab vedotin, nivolumab)Experimental Treatment6 Interventions
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Group V: Phase I Arm I (brentuximab vedotin, ipilimumab)Experimental Treatment6 Interventions
Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.

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 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.
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 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]
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

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]
Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial. [2023]
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]
Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. [2021]
A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma. [2019]
Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. [2021]
[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]
[Brentuximab vedotin: new treatment for CD30+ lymphomas]. [2019]
Brentuximab vedotin in systemic T-cell lymphoma. [2022]
Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. [2020]
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]
12.United Statespubmed.ncbi.nlm.nih.gov
Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. [2023]
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