Brentuximab + Chemotherapy + Radiation for Hodgkin Lymphoma

Not currently recruiting at 5 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Cd30 negative, Prior therapy, 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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a combination of treatments against Hodgkin lymphoma, a cancer affecting the lymphatic system. The study uses brentuximab vedotin, a monoclonal antibody targeting cancer cells, alongside chemotherapy drugs and possibly radiation therapy. The goal is to determine if this combination can kill more cancer cells and reduce the need for radiation. The trial seeks younger patients diagnosed with advanced stages of Hodgkin lymphoma who have not yet undergone treatment, though they may have received limited emergency therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 patients with Hodgkin lymphoma. In studies, the most common serious side effects included low white blood cell counts (neutropenia), low red blood cell counts (anemia), and low platelet counts (thrombocytopenia), affecting about 24%, 20%, and 16% of patients, respectively.

Etoposide has treated cancer for many years, and while it can cause various side effects, they are usually manageable. Doxorubicin, another long-standing cancer drug, is safe for many patients but can sometimes cause serious side effects like heart problems.

Cyclophosphamide, a common chemotherapy drug, works well but can lead to side effects such as low blood cell counts and a higher risk of infections. Dacarbazine is often included in treatment plans and is effective, though it can cause side effects like nausea and low blood cell counts.

This trial is in phase 2, indicating that some safety data is already available. The goal is to evaluate how well this combination of treatments works and to monitor any side effects. Each drug has its own safety profile, but they are part of widely used cancer treatments, indicating a known level of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for Hodgkin Lymphoma because it combines brentuximab vedotin with traditional chemotherapy agents like cyclophosphamide, dacarbazine, and doxorubicin. Brentuximab vedotin is an antibody-drug conjugate that specifically targets CD30-positive cancer cells, which makes it different from standard chemotherapies that affect both healthy and cancerous cells. This targeted approach could potentially reduce side effects and improve effectiveness. Additionally, integrating radiation therapy for non-responsive lymph nodes offers a tailored treatment strategy, addressing individual patient responses more precisely.

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

Research has shown that brentuximab vedotin, which participants in this trial may receive, effectively treats Hodgkin lymphoma. Studies have found it can help up to 86% of patients with recurring or hard-to-treat cases. Cyclophosphamide and dacarbazine, also part of the treatment regimen in this trial, have proven effective, with cyclophosphamide benefiting up to 73.5% of certain patient groups. Doxorubicin and etoposide, included in the trial's treatment arms, contribute to successful treatments, with doxorubicin leading to high cure rates and etoposide showing promising results in treating lymphoma. These drugs work in different ways to stop cancer cells from growing and help patients achieve long-term remission. ^{1 5 6 7 8}

Who Is on the Research Team?

Matt Ehrhardt, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young patients (up to 18 years old) with stage IIB, IIIB, or IV Hodgkin lymphoma that hasn't been treated yet. They must have a certain type of cancer cell called CD30+ and their kidneys and liver need to be working well. Girls after puberty must not be pregnant and all participants who can have children should agree to use birth control during the study.

Inclusion Criteria

I have Hodgkin Lymphoma that hasn't been treated yet, but I may have had emergency radiation or steroids for a short time.

My kidney function is good based on tests.

My liver tests are within the normal range for my age.

Exclusion Criteria

I have previously been treated for Hodgkin lymphoma.

My organs are not functioning properly.

I am unable or unwilling to give my consent to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

AEPA Chemotherapy

Participants receive brentuximab vedotin, etoposide, prednisone, and doxorubicin hydrochloride. Treatment repeats every 28 days for 2 courses.

8 weeks

Multiple visits for drug administration

CAPDac Chemotherapy

Participants receive cyclophosphamide, brentuximab vedotin, prednisone, and dacarbazine. Treatment repeats every 21-28 days for 4 courses.

12-16 weeks

Multiple visits for drug administration

Radiation Therapy

Participants with lymph nodes not in remission after 2 courses of AEPA undergo radiation therapy daily, 5 days a week.

3-4 weeks

Daily visits for radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 6 years

Every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Cyclophosphamide
• Dacarbazine
• Doxorubicin
• Etoposide
• Filgrastim
• Radiation Therapy

Trial Overview The trial tests if brentuximab vedotin combined with chemotherapy drugs (etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, dacarbazine) plus radiation therapy is effective in treating Hodgkin lymphoma in youth. It looks at how these treatments work together to stop cancer from growing.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 9 Interventions

Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). Filgrastim may be given as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy will be given. Some participants may volunteer to complete the quality of life assessment.

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?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

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

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]

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 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]

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, an antibody-drug conjugate, shows a high response rate of 75% in relapsed/refractory Hodgkin lymphoma, but resistance often develops due to upregulation of the MDR1 protein.

Combining brentuximab vedotin with cyclosporine A (CsA) effectively restores sensitivity to the drug in resistant cases, achieving a 75% overall response rate and 42% complete response rate in a phase I trial, indicating a promising new strategy to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma. Chen, R., Herrera, AF., Hou, J., 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3627331/

Safety and efficacy of brentuximab vedotin in patients with ... In phase II studies, brentuximab vedotin induced overall response rates of 75% and 86% in relapsed or refractory Hodgkin lymphoma and anaplastic large cell ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206125

Overall Survival with Brentuximab Vedotin in Stage III or IV ... The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group.

3. nature.com nature.com/articles/s41409-025-02557-7

Real-world outcomes of brentuximab vedotin as ... - Nature Hodgkin lymphoma (HL) has a high cure rate, with more than 80% of patients with classic HL achieving long-term remission following first-line ...

4. adcetris.com adcetris.com/classical-hodgkin-lymphoma/about-adcetris/

How may I benefit from ADCETRIS? ADCETRIS was an effective treatment for classical Hodgkin lymphoma that has a high risk of coming back or getting worse after a stem cell transplant.

5. ashpublications.org ashpublications.org/bloodadvances/article/7/24/7485/497552/Impact-of-cumulative-dose-of-brentuximab-vedotin

Impact of cumulative dose of brentuximab vedotin on ... In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with ...

6. adcetrispro.com adcetrispro.com/classical-hodgkin-lymphoma-post-auto-hsct-consolidation/efficacy

ADCETRIS® (brentuximab vedotin) Efficacy Data - Safety Info Brentuximab vedotin (ADCETRIS) is recommended by the NCCN Guidelines as a Category 2A treatment option for 1 year of post-auto-HSCT consolidation treatment.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3731651/

Safety and efficacy of brentuximab vedotin for Hodgkin ... The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03646123

NCT03646123 | Clinical Trial of Brentuximab Vedotin in ... 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 ...