Brentuximab Vedotin + Nivolumab for Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
Must not be taking: Corticosteroids, Immunosuppressives, others
Disqualifiers: CNS involvement, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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.
12345Is 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.
25678How 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.
1491011Eligibility 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
My kidneys are working well enough, as shown by a test.
My diagnosis is classical Hodgkin lymphoma, not the nodular type, confirmed by a specialist.
I am able to get out of my bed or chair and move around.
I have had only one previous treatment for my condition, excluding radiotherapy.
Exclusion Criteria
I have had progressive multifocal leukoencephalopathy in the past.
My cervical cancer is in its early stages and has not spread.
I do not have active lung inflammation or scarring.
I have vitiligo.
I have not received a live vaccine in the last 30 days.
I take more than 10 mg of prednisone daily without having an active autoimmune disease.
My lymphoma is causing my body to destroy red blood cells.
I had skin cancer (not melanoma) and was treated to cure it.
My psoriasis can be managed without strong medication.
I experience significant numbness or pain in my hands or feet.
My lymphoma has spread to my brain or spinal cord.
I have been diagnosed with an immune system disorder.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (brentuximab vedotin, nivolumab)Experimental Treatment2 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Sarah Cannon Research InstituteNashville, TN
City of Hope Medical CenterDuarte, CA
University of Chicago Cancer Research CenterChicago, IL
Dana-Farber Cancer InstituteBoston, MA
More Trial Locations
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Who is running the clinical trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
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]Recognising that the immune suppressive microenvironment promotes tumour growth in Hodgkin lymphoma, we hypothesised that activating immunity might augment the activity of targeted chemotherapy. We evaluated the safety and activity of combinations of brentuximab vedotin with nivolumab or ipilimumab, or both in patients with relapsed or refractory Hodgkin lymphoma.
Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. [2020]Intravenous brentuximab vedotin (ADCETRIS®) is a targeted antibody-drug conjugate (ADC) active against CD30-positive cancer cells such as those associated with classical Hodgkin lymphoma (HL). In noncomparative, phase 2 trials and in the real-world setting, salvage therapy with brentuximab vedotin resulted in high objective response (complete plus partial remission) rates in patients with relapsed or refractory CD30-positive HL, including as retreatment in patients who had an objective response to previous brentuximab vedotin therapy and subsequently relapsed. These beneficial outcomes were durable during long-term follow-up. As consolidation therapy after autologous haematopoietic stem cell transplant (ASCT) in the multinational, phase 3 AETHERA trial, brentuximab vedotin prolonged progression-free-survival (PFS) compared with placebo at a median follow-up of 30 months (primary analysis), with a 43% reduction in the risk of disease progression or death. The beneficial effects of brentuximab vedotin consolidation therapy were maintained during long-term follow-up. In the clinical trial and real-world setting, brentuximab vedotin had an acceptable tolerability and safety profile, with most adverse events manageable with dose reductions and/or delays [including peripheral sensory neuropathy (PSN) and neutropenia]. With a paucity of treatments available for many patients with relapsed or refractory HL, brentuximab vedotin represents an important option for the management of patients who have failed high-dose chemotherapy/ASCT or at least two prior chemotherapy regimens and as post-ASCT consolidation therapy in patients who are at increased risk/high-risk of relapse or progression after ASCT.
Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. [2022]Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.
Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. [2023]Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma.
Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. [2021]Brentuximab vedotin (ADCETRIS(®)) is an antibody-drug conjugate that is specifically targeted against CD30-positive cancer cells such as those in Hodgkin lymphoma or systemic anaplastic large cell lymphoma (ALCL). Intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 75 % in 102 patients with Hodgkin lymphoma who had relapsed after high-dose chemotherapy and autologous haematopoietic stem cell transplantation, in a noncomparative, multicentre, phase II trial. In 58 patients with relapsed systemic ALCL after at least one prior treatment, intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 86 % in a noncomparative, multicentre, phase II trial. Tumour reductions were observed in 94 % of patients with Hodgkin lymphoma and 97 % of patients with systemic ALCL, and most tumours decreased in size by >65 % and >85 %, respectively. The estimated 12-month survival rates were 89 % and 52 %, respectively. Brentuximab vedotin was generally well tolerated in these trials. The most common adverse event was peripheral neuropathy; approximately one-half of patients with this adverse event experienced complete resolution.
[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.
Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. [2019]The antibody-drug conjugate (ADC) brentuximab vedotin consists of the CD30-directed antibody attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In pharmacokinetic models, including data from six studies (380 patients with classical Hodgkin's, systemic anaplastic large-cell, and cutaneous T-cell (CTCL) lymphomas), lower clearance of ADC and modestly higher ADC exposure in CTCL patients did not translate into higher MMAE exposure. In CTCL patients from the phase III ALCANZA study (n = 66), improved progression-free survival with brentuximab vedotin vs. controls was not related to ADC exposure. ADC exposure was a predictor of grade ≥3 treatment-emergent adverse events (TEAEs). Results support the consistent benefit observed with brentuximab vedotin 1.8 mg/kg every 3 weeks across the range of exposures in ALCANZA and support dose reductions in patients experiencing TEAEs at the starting dose.
A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma. [2019]Brentuximab vedotin is an anti-CD30 monoclonal antibody-drug conjugate approved for treating relapsed or refractory Hodgkin lymphoma. The pivotal trial demonstrated brentuximab vedotin's efficacy and manageable toxicity profile with peripheral neuropathy and neutropenia being the most common side effects. The phase I study of brentuximab vedotin combined with ABVD or AVD revealed its contraindication with bleomycin due to pulmonary toxicity. As trials continue to investigate the drug in frontline and relapsed settings, emerging safety data will further define brentuximab vedotin's role in managing Hodgkin lymphoma.
Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. [2020]Brentuximab vedotin is a Food and Drug Administration approved anti-CD30 antibody drug conjugate potently active in Hodgkin lymphoma. Trials of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (AVD-BV) excluded patients with HIV. We studied the safety of AVD-BV in newly diagnosed HIV-associated classical Hodgkin lymphoma .
Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. [2023]Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure.
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]Hodgkin lymphoma is potentially curable. However, 15-35% of older patients (ie, >60 years) have a lower response rate, worse survival outcomes, and greater toxicity than younger patients. Brentuximab vedotin and nivolumab exhibit activity in patients with relapsed or refractory Hodgkin lymphoma. We therefore aimed to evaluate the safety and efficacy of brentuximab vedotin and nivolumab in untreated older patients with Hodgkin lymphoma or in younger patients considered unsuitable for standard ABVD (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy.