Brentuximab Vedotin + Chemotherapy for Hodgkin's Lymphoma

Not currently recruiting at 221 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic corticosteroids

Disqualifiers: Immunodeficiency, Pregnancy, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if adding brentuximab vedotin to standard chemotherapy treats Hodgkin lymphoma in children and young adults more effectively than chemotherapy alone. Brentuximab vedotin delivers cancer-killing substances directly to lymphoma cells. Participants will receive either standard chemotherapy or chemotherapy combined with brentuximab vedotin. This trial suits those newly diagnosed with certain advanced stages of Hodgkin lymphoma who have not yet received treatment. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have received any previous chemotherapy, radiation therapy, or systemic corticosteroids within 28 days before enrolling.

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

Research has shown that brentuximab vedotin is generally well-tolerated by people with Hodgkin lymphoma. One study reported serious side effects, including low white blood cell counts in 24% of patients, low red blood cell counts in 20%, and low platelet counts in 16%. Another study found high survival rates after six years, suggesting the treatment might be safe for long-term use.

The chemotherapy drugs used in this trial, such as doxorubicin and bleomycin, are standard treatments for Hodgkin lymphoma. They can cause side effects like nausea, hair loss, and tiredness, which are usually manageable.

Overall, while side effects exist, this treatment has been used in other settings, providing some evidence of its safety. Anyone considering joining the trial should discuss these risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Hodgkin's lymphoma?

Researchers are excited about Brentuximab Vedotin for Hodgkin's Lymphoma because it introduces a targeted approach by delivering a potent chemotherapy agent directly to cancer cells. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, Brentuximab Vedotin links an antibody to a chemotherapy drug, specifically targeting the CD30 protein found on Hodgkin's Lymphoma cells. This method aims to reduce side effects and increase the effectiveness of treatment. Moreover, combining Brentuximab Vedotin with standard chemotherapy agents like doxorubicin and cyclophosphamide could enhance treatment outcomes by leveraging both targeted and broad-spectrum cancer-fighting strategies.

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

Research has shown that adding brentuximab vedotin to chemotherapy can help patients with advanced Hodgkin lymphoma live longer. In this trial, participants in Arm II will receive this combination treatment, which previous studies have shown to achieve a 6-year survival rate of 93.9%. In contrast, Arm I participants will receive only chemotherapy, which similar studies have shown to have a 6-year survival rate of 89.4%. Brentuximab vedotin directly targets and kills cancer cells, providing a focused treatment. Medical guidelines also recommend it for certain stages of Hodgkin lymphoma. These findings suggest that combining brentuximab vedotin with chemotherapy may offer a more effective option for treating high-risk Hodgkin lymphoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Sharon M Castellino

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults with newly diagnosed Hodgkin lymphoma stages IIB (with bulk), IIIB, IVA, or IVB. Participants must have proper kidney function, normal bilirubin levels, healthy liver enzymes, good heart function, and acceptable lung capacity. They cannot join if they have certain types of immunodeficiency, are pregnant or breastfeeding, HIV positive, or have had previous cancer treatments.

Inclusion Criteria

My lung function test shows I breathe well enough, unless it's due to a large chest tumor from Hodgkin Lymphoma.

My lung function test shows I can breathe out well.

Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by radionuclide angiogram

Exclusion Criteria

Lactating females who plan to breastfeed

Sexually active patients of reproductive potential who have not agreed to use effective contraception

I have not taken systemic corticosteroids in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin and combination chemotherapy or combination chemotherapy alone for 5 cycles, each cycle lasting 21 days

15 weeks

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Follow-up visits at 3, 6, 9, 12, 18, 24, 30, 36, and 48 months

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Etoposide
• Methylprednisolone
• Prednisone
• Vincristine Sulfate

Trial Overview

The study is testing the effectiveness of brentuximab vedotin combined with chemotherapy against chemotherapy alone in treating high-risk Hodgkin lymphoma. The goal is to see if adding brentuximab vedotin improves treatment outcomes by targeting cancer cells more directly.

How Is the Trial Designed?

Group I: ARM II (Bv-AVEPC) Experimental Treatment 11 Interventions

Patients receive brentuximab vedotin IV on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and cyclophosphamide as in Arm I and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (ABVE-PC) Active Control 11 Interventions

Patients receive doxorubicin hydrochloride IV over on days 1-2, bleomycin sulfate IV or SC on days 1 and 8, vincristine sulfate IV on days 1 and 8, etoposide IV on days 1-3, prednisone orally PO BID or methylprednisolone IV on days 1-7, and cyclophosphamide IV on days 1 and 2. Treatment repeats every 21 days for 5 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

In a study involving 104 patients with advanced classical Hodgkin's lymphoma, both modified eBEACOPP regimens (BrECAPP and BrECADD) achieved high rates of complete response (86% and 88%, respectively) and complete remission, demonstrating their efficacy in treating this condition.

The BrECADD regimen showed a more favorable safety profile with fewer severe organ toxic effects compared to BrECAPP, making it a promising candidate for further testing against standard treatments in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group. Eichenauer, DA., Plütschow, A., Kreissl, S., et al.[2019]

In a study involving 65 heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma and anaplastic large-T-cell lymphoma, the combination of brentuximab vedotin and bendamustine showed a high overall response rate of 78%, indicating its efficacy as a salvage treatment.

The treatment demonstrated a favorable safety profile, with no treatment-related deaths and manageable side effects, making it a potential alternative to traditional platinum-based chemotherapy before autologous stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. O'Connor, OA., Lue, JK., Sawas, A., et al.[2022]

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 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]

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 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 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]

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This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky ...