Brentuximab +/− Nivolumab for Lymphoma

Overseen By Ajay K. Gopal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Brentuximab vedotin

Must not be taking: Other anti-cancer agents

Disqualifiers: HIV, Hepatitis B, CNS involvement, 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: Unknown

Duration: 12-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments, brentuximab vedotin and nivolumab, for individuals with CD30+ lymphoma that has returned or isn't responding to other treatments. Brentuximab vedotin, an antibody-drug conjugate, may boost the immune system to fight cancer, while nivolumab, an immunotherapy drug, might help stop cancer cells from growing and spreading. Participants will receive either brentuximab vedotin alone or in combination with nivolumab to determine which works better. The trial targets those whose CD30+ lymphoma has returned after treatment or hasn't improved with previous brentuximab vedotin therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot use other anti-cancer agents or experimental treatments while participating in this trial.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot use other anti-cancer agents or experimental treatments while participating in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that brentuximab vedotin is generally well-tolerated by patients with CD30-positive lymphomas. Common side effects included low white blood cell count in 24% of patients and low red blood cell count in 20%. Although these numbers might seem high, medical care can manage them.

When combined with nivolumab, brentuximab vedotin maintained an acceptable safety profile. Research showed that 85% of patients responded well to the treatment, indicating positive results for most. The combination was generally well-tolerated, allowing patients to receive additional treatments like stem cell transplants without major issues.

Overall, both brentuximab vedotin alone and with nivolumab have demonstrated promising safety results in previous trials. While side effects can occur, they are often manageable, and the treatments have been effective for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Brentuximab Vedotin and Nivolumab for lymphoma because it offers a novel approach by integrating an antibody-drug conjugate with an immune checkpoint inhibitor. Brentuximab Vedotin targets CD30 on lymphoma cells, delivering a potent drug directly to the cancer cells, while Nivolumab helps the immune system recognize and attack the cancer by blocking the PD-1 pathway. This dual action not only aims to directly kill cancer cells but also enhances the body's own immune response against the tumor, potentially leading to improved outcomes compared to traditional chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for CD30+ lymphoma?

Research has shown that brentuximab vedotin effectively treats CD30-positive lymphomas, particularly when the cancer recurs or resists other treatments. One study found that this treatment helped shrink tumors and provided long-lasting results for many patients, with some remaining cancer-free for over five years. In this trial, participants in Arm A will receive brentuximab vedotin alone.

Arm B will test the combination of brentuximab vedotin with nivolumab, a drug that helps the immune system fight cancer. Studies have shown encouraging results for this combination, with one study reporting that the cancer became undetectable in 95% of patients. These findings suggest that these treatments can be strong options for managing CD30-positive lymphomas. ^{2 5 6 7 8}

Who Is on the Research Team?

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with CD30+ lymphoma that has returned or isn't responding to treatment. They must have certain blood counts, kidney and liver function within set limits, and a life expectancy over 90 days without treatment. Not eligible if they have significant neuropathy, intolerance to brentuximab vedotin, poor performance status, recent transplants or radioimmunotherapy, HIV/hepatitis B infection, pregnancy/breastfeeding without contraception use.

Inclusion Criteria

Platelets > 50,000/uL

Expected survival if untreated of > 90 days

All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines

Exclusion Criteria

Intolerance to brentuximab vedotin

I have not had a transplant in the last 100 days.

My daily activity is significantly limited due to my health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive brentuximab vedotin with or without nivolumab. Arm A: brentuximab vedotin IV on days 1, 8, and 15 every 28 days for up to 4 courses. Arm B: brentuximab vedotin and nivolumab IV on day 1 every 21 days for up to 4 courses.

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up at 3-5 weeks, every 3 months for 1 year, then every 6 months for 4 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Nivolumab

Trial Overview

The study tests how well the drug Brentuximab Vedotin works alone or combined with Nivolumab in patients whose CD30+ lymphoma has relapsed or is refractory. It examines whether these treatments can stimulate the immune system to stop cancer growth more effectively than current methods.

How Is the Trial Designed?

Group I: Arm B (brentuximab vedotin, nivolumab) Experimental Treatment 3 Interventions

Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (brentuximab vedotin) Experimental Treatment 2 Interventions

Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses 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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

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]

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, 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 is an effective treatment for relapsed or refractory Hodgkin lymphoma and other CD30-positive cancers, showing durable antitumor activity with a manageable safety profile.

The main side effect of brentuximab vedotin is peripheral sensory neuropathy, which is dose-related and cumulative, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. van de Donk, NW., Dhimolea, E.[2023]

In the international phase III ALCANZA trial, brentuximab vedotin, a CD30-directed antibody-drug conjugate, showed significantly better clinical responses in patients with cutaneous T-cell lymphomas compared to standard treatments like methotrexate or bexarotene.

This study highlights the efficacy of brentuximab vedotin as a more effective treatment option for patients with this type of lymphoma, suggesting a promising advancement in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Beats Standard Therapies for CTCL. [2019]

Brentuximab vedotin, an antibody-drug conjugate, does not cause significant prolongation of the QT/QTc interval, indicating a favorable cardiac safety profile in patients with CD30-positive hematologic malignancies.

In a phase 1 study involving 52 patients, brentuximab vedotin was well tolerated, with no clinically meaningful changes in cardiac repolarization and a response rate consistent with previous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. Han, TH., Chen, R., Advani, R., et al.[2021]

In a review of 2225 lymphoma patients from 4 randomized controlled trials, brentuximab vedotin was found to significantly increase the risk of all-grade adverse events (AEs) and high-grade AEs compared to non-brentuximab vedotin treatments.

Specific AEs associated with brentuximab vedotin included a higher risk of peripheral sensory neuropathy, pyrexia, nausea, vomiting, diarrhea, and alopecia, with particularly high risks for high-grade sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Gao, S., Zhang, M., Wu, K., et al.[2021]

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 antibody-drug conjugate that combines an anti-CD30 antibody with a powerful cytotoxic agent, showing promise in treating Hodgkin lymphoma and anaplastic large cell lymphoma.

The drug is currently under investigation in North America and Europe, highlighting its potential as a targeted therapy for specific types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, shows promise in treating relapsed or refractory B-cell non-Hodgkin lymphomas, particularly when combined with rituximab and bendamustine, as indicated by early clinical data.

The ongoing phase III POLARIX trial is exploring its effectiveness in first-line treatment for untreated patients, with careful management of dosing to minimize the risk of peripheral neuropathy, potentially making it a key player in DLBCL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma. Bourbon, E., Salles, G.[2022]

Brentuximab vedotin (BV) is an effective treatment for relapsed or refractory Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL), and it has recently been approved for use as a consolidation therapy after autologous stem cell transplantation in high-risk HL patients.

BV is being investigated in various new treatment settings, including as a single agent or in combination with other therapies for first-salvage HL and frontline treatment in DLBCL, showing promising results that could lead to first-line approvals if ongoing trials are successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New uses for brentuximab vedotin and novel antibody drug conjugates in lymphoma. Merli, M., Ferrario, A., Maffioli, M., et al.[2019]

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]

Brentuximab vedotin (BV) has shown promising efficacy in treating refractory CD30+ non-Hodgkin lymphomas (NHL), as demonstrated in two cases where patients responded positively to BV-based regimens after failing multiple standard treatments.

Both patients, one with anaplastic large cell lymphoma and the other with diffuse large B-cell lymphoma, experienced significant responses to novel BV combinations, suggesting that these regimens are effective and have manageable side effects, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature. Delacruz, W., Setlik, R., Hassantoufighi, A., et al.[2020]

Brentuximab vedotin demonstrated a high overall response rate of 73% and a complete response rate of 35% in 48 patients with CD30(+) cutaneous T-cell lymphomas, indicating its efficacy as a treatment option.

The treatment was generally well tolerated, with most adverse effects being grade 1 to 2 peripheral neuropathy observed in 65% of patients, while serious side effects were relatively rare, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. Duvic, M., Tetzlaff, MT., Gangar, P., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5034737/

Five-year survival and durability results of brentuximab ...

A total of 38% of patients who achieved CR (13 of 34) on brentuximab vedotin have remained in remission for >5 years and may be cured. Nine of the 13 patients ( ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40200006/

Real-world outcomes of brentuximab vedotin as ...

Brentuximab vedotin (BV) as post-autologous stem cell transplantation (ASCT) consolidation was shown to reduce the relapse risk among high-risk patients.

3.

adcetrispro.com

adcetrispro.com/classical-hodgkin-lymphoma-post-auto-hsct-consolidation/efficacy

ADCETRIS® (brentuximab vedotin) Efficacy Data - Safety Info

AETHERA primary endpoint: PFS* per IRF · HR: 0.57 (95% CI: 0.40, 0.81); P = 0.001 · 18.8 months median PFS benefit. 42.9† months with ADCETRIS (95% Cl: 30.4, 42.9) ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1002965

Brentuximab Vedotin (SGN-35) for Relapsed CD30- ...

Brentuximab vedotin induced durable objective responses and resulted in tumor regression for most patients with relapsed or refractory CD30-positive lymphomas.

5.

ashpublications.org

ashpublications.org/bloodadvances/article/7/24/7485/497552/Impact-of-cumulative-dose-of-brentuximab-vedotin

Impact of cumulative dose of brentuximab vedotin on ...

In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3731651/

Safety and efficacy of brentuximab vedotin for Hodgkin ...

The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3627331/

Safety and efficacy of brentuximab vedotin in patients with ...

In phase II studies, brentuximab vedotin induced overall response rates of 75% and 86% in relapsed or refractory Hodgkin lymphoma and anaplastic large cell ...

8.

adcetris.com

adcetris.com/classical-hodgkin-lymphoma/about-adcetris/

How may I benefit from ADCETRIS?

Overall survival rate was higher with ADCETRIS plus AVD compared to ABVD chemotherapy · The following data represent the overall survival that was observed at 6 ...