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

Trial Summary

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.

What data supports the effectiveness of the drug Brentuximab vedotin (Adcetris) for treating Hodgkin's Lymphoma?

Brentuximab vedotin has shown a high response rate in patients with relapsed Hodgkin lymphoma, with 75% of patients responding to the treatment in a study. Additionally, it has been effective in prolonging progression-free survival when used as a consolidation therapy after stem cell transplant, reducing the risk of disease progression or death by 43%. ^{1 2 3 4 5}

Is Brentuximab vedotin (BV-AVD) safe for humans?

Brentuximab vedotin, used in treating Hodgkin lymphoma, is generally well tolerated with manageable side effects. Common side effects include peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count), but these are often resolved with dose adjustments. ^{1 2 3 5 6}

What makes the drug Brentuximab vedotin (Adcetris) unique for treating Hodgkin's Lymphoma?

Brentuximab vedotin is unique because it is an antibody-drug conjugate that specifically targets CD30-positive cancer cells, which are common in Hodgkin's Lymphoma. It combines a monoclonal antibody with a powerful cancer-killing agent, offering a targeted approach that can be effective even when other treatments have failed. ^{1 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to test whether BV-AVD is an effective treatment in people with early stage, bulky Hodgkin lymphoma that was recently diagnosed and who have not yet received any treatments for their disease. BV is a type of drug called an antibody-drug conjugate (ADC). ADCs are a substance made up of a monoclonal antibody chemically linked to a drug. Antibodies are proteins made by the immune system to fight infections and other possible harms to the body. The monoclonal antibody binds to specific proteins or receptors found on certain types of cells, including cancer cells. The linked drug enters these cells and kills them without harming other cells. Researchers think BV may be an effective treatment for this type of cancer because the drug targets cells that have CD30, which play a role in cancer cell growth. By destroying these cells, BV may help slow or stop the growth of the cancer. AVD (doxorubicin, vinblastine, and dacarbazine) is a treatment regimen that works by stopping the growth of cancer cells, either by killing the cells or by stopping them from dividing. The researchers think that BV in combination with AVD may work better than AVD alone to slow or stop the growth of the cancer.

Research Team

Robert Stuver, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. New Zealand 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. [2021]

2. United States 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. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Management of relapsed or refractory hodgkin lymphoma with second-generation antibody-drug conjugates: focus on brentuximab vedotin. [2021]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma. [2019]

7. England 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. [2019]

8. England 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. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. [2019]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Role of brentuximab vedotin in the treatment of relapsed or refractory Hodgkin lymphoma. [2021]