Brentuximab + Chemotherapy for Hodgkin's Lymphoma

Recruiting at 217 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Millennium Pharmaceuticals, Inc.

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

1334 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin \[Adriamycin\], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin \[Adriamycin\],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have had prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of the first study drug dose, you may not be eligible to participate.

Is the combination of Brentuximab and chemotherapy safe for treating Hodgkin's Lymphoma?

The combination of Brentuximab with chemotherapy for Hodgkin's Lymphoma has shown some safety concerns. Common side effects include peripheral neuropathy (nerve damage causing tingling or numbness), neutropenia (low white blood cell count), fatigue, and nausea. In some cases, severe side effects like febrile neutropenia (fever with low white blood cell count) and neutropenic sepsis (a serious infection due to low white blood cells) have occurred, especially in older patients. ^{1 2 3 4 5}

What makes the drug Brentuximab Vedotin combined with chemotherapy 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. This targeted approach, combined with chemotherapy, has shown high response rates and is particularly beneficial for patients who have relapsed after other treatments. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Brentuximab Vedotin combined with chemotherapy for treating Hodgkin's Lymphoma?

Research shows that Brentuximab Vedotin combined with chemotherapy (AVD+BV) reduces the risk of disease progression in advanced Hodgkin lymphoma compared to standard chemotherapy. Additionally, it has shown high response rates in relapsed or refractory cases and prolonged progression-free survival when used as consolidation therapy after stem cell transplant. ^{2 6 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for individuals with advanced classical Hodgkin Lymphoma who have measurable disease, are relatively active (ECOG <=2), and haven't started treatment yet. They must be diagnosed at a late stage (III or IV) according to Ann Arbor staging and confirmed by WHO classification.

Inclusion Criteria

My diagnosis is classical Hodgkin Lymphoma according to WHO standards.

I have Stage III or IV Hodgkin's lymphoma and haven't received any treatment.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have been diagnosed with a type of lymphoma called nodular lymphocyte predominant Hodgkin lymphoma.

I do not have brain or spinal cord disease, including PML.

I have nerve damage affecting my senses or movement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either A+AVD or ABVD regimen for frontline treatment of advanced classical Hodgkin lymphoma

1 year

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Bleomycin
• Brentuximab Vedotin
• Dacarbazine
• Doxorubicin
• Vinblastine

Trial Overview The study compares two treatments: A+AVD (brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine) against ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). It's designed to see which combination better prevents the cancer from progressing without getting worse.

How Is the Trial Designed?

Group I: A + AVD Experimental Treatment 4 Interventions

A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.

Group II: ABVD Active Control 4 Interventions

ABVD consists of doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.

Bleomycin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Approved in United States as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Approved in Canada as Bleomycin for:

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Ovarian cancer
• Malignant pleural effusions

Who Is Running the Clinical Trial?

Millennium Pharmaceuticals, Inc.

Lead Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

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

A systematic review of 62 randomized controlled trials found that the five-year overall survival rates for ABVD and BEACOPP regimens in advanced-stage Hodgkin lymphoma were 60-97% and 84-99%, respectively, indicating high efficacy for both treatments.

The new treatment A+AVD showed improved efficacy compared to ABVD while maintaining an acceptable tolerability profile, suggesting it may be a more manageable option for patients with advanced-stage Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. Dalal, M., Gupta, J., Price, K., 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.

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 (BV) combined with doxorubicin, vinblastine, and dacarbazine (AVD+BV) improves clinical outcomes in adults with stage III or IV Hodgkin lymphoma, providing an increase of 0.56 quality-adjusted life-years (QALYs) compared to standard ABVD therapy.

However, the use of BV significantly raises lifetime healthcare costs, resulting in an incremental cost-effectiveness ratio (ICER) of $317,254 per QALY, indicating that it is unlikely to be cost-effective at current pricing without substantial price reductions for BV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma. Huntington, SF., von Keudell, G., Davidoff, AJ., et al.[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 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 of 34 patients with nonbulky stage I/II Hodgkin lymphoma, the combination of brentuximab vedotin and AVD (doxorubicin, vinblastine, dacarbazine) achieved a remarkable 100% complete response rate, with high progression-free survival (94%) and overall survival (97%) at a median follow-up of 38 months.

Despite the high efficacy, the treatment was associated with significant adverse effects, including high rates of peripheral sensory neuropathy (79%) and neutropenia (76%), leading to dose reductions in 38% of patients, suggesting that this regimen may not be suitable for early-stage patients with a favorable prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma. Abramson, JS., Arnason, JE., LaCasce, AS., et al.[2021]

In the phase III ECHELON-1 study involving 1,334 patients, older patients (aged ≥60) with classical Hodgkin lymphoma showed similar modified progression-free survival rates at 24 months when treated with brentuximab vedotin plus AVD (70.3%) compared to ABVD (71.4%).

While A+AVD demonstrated comparable efficacy to ABVD, it was associated with higher rates of grade 3/4 peripheral neuropathy (18% vs. 3%) and febrile neutropenia (37% vs. 17%), but lower rates of pulmonary toxicity, with no pulmonary-related deaths in the A+AVD group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Evens, AM., Connors, JM., Younes, A., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study. [2022]

3. 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]

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

Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma. [2019]

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

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

6. 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]

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

Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. [2021]

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

Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. [2022]