BV-AVD for Hodgkin's Lymphoma

Recruiting at 7 trial locations

Overseen By Alison Moskowitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Antiretrovirals

Must not be taking: Zidovudine, Ritonavir, CYP3 inhibitors

Disqualifiers: Pregnancy, Cardiac issues, Autoimmune, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

71 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with early-stage, bulky Hodgkin lymphoma, a cancer affecting the lymphatic system. The treatment includes BV (Brentuximab vedotin), an antibody-drug conjugate that targets and kills cancer cells, combined with a chemotherapy regimen known as AVD. Researchers aim for this combination to be more effective than traditional treatments in stopping cancer growth. Individuals recently diagnosed with CD30-positive Hodgkin lymphoma, who have significant lymph node masses and have not yet started treatment, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on certain HIV medications like zidovudine or ritonavir, you must switch to a different regimen 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that BV-AVD is likely to be safe for humans?

Research has shown that brentuximab vedotin (BV) is generally well-tolerated by patients with Hodgkin lymphoma. Studies have found that BV, when combined with AVD chemotherapy, is usually safe.

In one study, long-term follow-up revealed that most patients experienced manageable side effects, including low blood cell counts, tiredness, and some nerve damage. Serious side effects were less common but included infections and low blood cell counts requiring medical attention.

Another study confirmed that while some patients experienced severe side effects, these were relatively rare. Most side effects were mild to moderate and could be treated or managed effectively.

Overall, past patients demonstrated that BV combined with AVD can be safely administered with careful monitoring and support. However, like any treatment, discussing potential risks with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for Hodgkin's Lymphoma?

Researchers are excited about BV-AVD for Hodgkin's Lymphoma because it incorporates brentuximab vedotin, which targets the CD30 protein on cancer cells. This approach is different from traditional chemotherapy regimens like ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), as it combines targeted therapy with chemotherapy. Additionally, the study uses PET scans to tailor the treatment based on how well the cancer responds after just two cycles, potentially minimizing unnecessary treatment. This personalized approach aims to improve outcomes and reduce side effects compared to the standard of care.

What evidence suggests that BV-AVD might be an effective treatment for Hodgkin's lymphoma?

Research has shown that brentuximab vedotin (BV) holds promise for treating Hodgkin lymphoma. In this trial, all participants will receive BV combined with AVD, a mix of doxorubicin, vinblastine, and dacarbazine. Studies have found that this combination can improve survival rates. Specifically, in a study on advanced Hodgkin lymphoma, the survival rate was about 93.9% with BV-AVD, compared to 89.4% with a similar treatment without BV. This finding suggests that adding BV might be more effective than traditional treatments alone. BV targets cancer cells with a specific protein called CD30, which helps slow or stop cancer growth. This targeted approach may make BV-AVD a strong option for treating this type of cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Robert Stuver, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people who have just been diagnosed with early stage, bulky Hodgkin lymphoma and haven't started treatment yet. They should be able to undergo the treatments being tested.

Inclusion Criteria

My Hodgkin lymphoma is CD30-positive as confirmed by my hospital.

My lymph node mass is larger than 7 cm as shown on a CT scan.

My lymphoma is in the early stages and shows up on special body scans.

Exclusion Criteria

I am on continuous medication for an autoimmune disease.

Platelet count ≤ 75,000/µL

Absolute neutrophil count ≤ 1.0 K/µL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 cycles of BV-AVD chemotherapy, followed by a PET scan to assess response. Depending on the PET scan results, additional cycles of BV-AVD may be administered, with or without radiation therapy.

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab vedotin

Trial Overview

The study tests BV-AVD, a combination of an antibody-drug conjugate called Brentuximab vedotin (BV) and chemotherapy drugs doxorubicin, vinblastine, and dacarbazine (AVD). It aims to see if this mix works better than standard therapy in treating Hodgkin lymphoma.

How Is the Trial Designed?

Group I: BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) Experimental Treatment 8 Interventions

All patients will receive 2 cycles of brentuximab vedotin (BV) in combination with AVD chemotherapy (doxorubicin, vinblastine, dacarbazine). Prophylactic growth factor support will be mandated with each cycle. After 2 cycles of therapy, patients will undergo FDG-PET/CT scan (PET2). Patients with disease progression (Deauville 4 or 5) will be taken off study. Patients who achieve a PETnegative scan (Deauville score of ≤ 3) will receive 2 additional cycles of BV-AVD with no further therapy. In those with partial response or stable disease (Deauville score of 4 or 5), patients will be stratified by baseline metabolic tumor volume (bMTV) as bMTV-high (\> 150 cm3 ) or bMTV-low (≤ 150 cm3 ) as measured on pre-treatment FDG-PET/CT. In the bMTV-low group, patients will receive an additional 2 cycles of BV-AVD in combination with radiation therapy.

Brentuximab vedotin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Approved in United States as Adcetris for:

• Classical Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• Mycosis fungoides

Approved in Canada as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma

Approved in Japan as Adcetris for:

• Hodgkin lymphoma
• Anaplastic large cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

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]

In a phase 2 study involving 41 patients with untreated HIV-associated classical Hodgkin lymphoma, brentuximab vedotin combined with AVD showed a high complete response rate of 100% among those who completed therapy, with a 2-year progression-free survival rate of 87%.

The treatment was generally well-tolerated, with the most common serious side effects being neutropenia and peripheral sensory neuropathy, indicating that brentuximab vedotin-AVD is a promising and safe option for patients with HIV-cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial. Rubinstein, PG., Moore, PC., Bimali, M., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 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]

Brentuximab vedotin (BV) is effective for treating relapsed or refractory CD30-positive Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, but there are still uncertainties about its optimal use in these and other conditions.

A consensus project by the Italian Society of Hematology and related organizations has provided recommendations on key issues such as testing for CD30 positivity, patient eligibility, monitoring treatment response, and potential use in other CD30-positive lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. Zinzani, PL., Corradini, P., Gianni, AM., et al.[2019]

Brentuximab vedotin (BV) is an effective treatment for relapsed or refractory classical Hodgkin lymphoma, showing a 75% overall response rate and a median remission duration of 20 months in pivotal Phase II studies.

BV has a manageable safety profile, with peripheral neuropathy being the most significant side effect, which is mostly reversible, making it a preferred option for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of brentuximab vedotin in the treatment of relapsed or refractory Hodgkin lymphoma. Siddiqi, T., Thomas, SH., Chen, R.[2021]

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]

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]

Brentuximab vedotin is an effective antibody-drug conjugate specifically targeting CD30-positive lymphomas, approved for treating relapsed Hodgkin lymphoma after stem-cell transplantation or two lines of chemotherapy.

It is also approved for relapsed anaplastic large-cell lymphoma, highlighting its significant role in managing these specific types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin. Mei, M., Thomas, S., Chen, R.[2021]

In a study of 136 patients with relapsed/refractory Hodgkin lymphoma who were ineligible for autologous stem cell transplant, brentuximab vedotin (BV) showed a high overall response rate of 74%, indicating its effectiveness in this population.

The median progression-free survival (PFS) and overall survival (OS) were 15.1 months and 17.8 months, respectively, with peripheral neuropathy reported in 9.6% of patients, highlighting the treatment's safety profile in elderly or frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma who are Ineligible for autologous stem cell transplant: A Germany and United Kingdom retrospective study. Bröckelmann, PJ., Zagadailov, EA., Corman, SL., et al.[2019]

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