Brentuximab Vedotin + Chemotherapy for Hodgkin's Lymphoma

Recruiting at 210 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

600 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 you cannot participate if you have received any previous chemotherapy, radiation therapy, or systemic corticosteroids within 28 days before enrolling.

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

Research shows that Brentuximab Vedotin is effective in treating relapsed Hodgkin's lymphoma and is well tolerated. When combined with chemotherapy, it aims to reduce side effects while maintaining effectiveness, as seen in modified treatment regimens like eBEACOPP. ^{1 2 3 4 5}

Is Brentuximab Vedotin safe for treating Hodgkin's Lymphoma?

Brentuximab Vedotin is generally well tolerated, but common side effects include peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count). These side effects are usually manageable, and no deaths have been linked to the drug's toxicity. ^{6 7 8 9 10}

What makes the drug Brentuximab Vedotin unique for treating Hodgkin's Lymphoma?

Brentuximab Vedotin is unique because it is an antibody-drug conjugate specifically targeting CD30-positive cancer cells, which are common in Hodgkin's lymphoma. It is incorporated into treatment regimens to reduce toxic effects while maintaining efficacy, and it has shown high response rates in patients who have relapsed after other treatments. ^{1 5 7 11 12}

What is the purpose of this trial?

This phase III trial studies brentuximab vedotin and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating children and young adults with stage IIB with bulk, stage IIIB, IVA, or IVB Hodgkin lymphoma. Combinations of biological substances in brentuximab vedotin may be able to carry cancer-killing substances directly to Hodgkin lymphoma cells. Chemotherapy drugs, such as doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if combination chemotherapy is more effective with or without brentuximab vedotin in treating children with high-risk Hodgkin lymphoma.

Research Team

Sharon M Castellino

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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 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 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 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]

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]

References

1. England 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. [2019]

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

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

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

Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B. [2017]

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

Safety and efficacy of single-agent bendamustine after failure of brentuximab vedotin in patients with relapsed or refractory hodgkin's lymphoma: experience with 27 patients. [2019]

6. France pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]

7. 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]

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

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

9. France pubmed.ncbi.nlm.nih.gov

[Brentuximab vedotin: new treatment for CD30+ lymphomas]. [2019]

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

Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program. [2019]

11. 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]

12. England 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. [2022]