Brentuximab Vedotin + Chemotherapy for Hodgkin's Lymphoma

Not currently recruiting at 19 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Millennium Pharmaceuticals, Inc.

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Neuropathy, HIV, Hepatitis B/C, others

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

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

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to evaluate their safety and effectiveness in treating advanced-stage classical Hodgkin's Lymphoma in children. Researchers aim to assess how well the combination of brentuximab vedotin (Adcetris, a type of targeted therapy) and three chemotherapy drugs works and to determine the optimal dose. This trial targets children newly diagnosed with advanced Hodgkin's Lymphoma who have not yet begun treatment. Participants should have CD30+ Hodgkin's Lymphoma at stage III or IV. As a Phase 1/Phase 2 trial, this research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group.

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 use certain strong or moderate CYP3A4 inhibitors within 2 weeks before starting the trial treatment.

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

Research has shown that brentuximab vedotin, combined with chemotherapy drugs like doxorubicin, vinblastine, and dacarbazine, has been tested in people with advanced Hodgkin's lymphoma. These studies found that this combination could extend patients' lives, but it also caused more side effects than some other treatments.

The side effects resemble those of typical chemotherapy and can include tiredness, nausea, and lower blood cell counts, which might increase infection risk. Despite these side effects, many patients managed the treatment well enough to experience significant benefits.

These results come from earlier studies. Current trials continue to assess the safety of this treatment, especially for children with newly diagnosed Hodgkin's lymphoma. Always consult a healthcare provider to understand what these findings mean for individual circumstances. ^{1 2 3 4 5}

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

Researchers are excited about using brentuximab vedotin with chemotherapy for Hodgkin's lymphoma because it targets cancer cells in a unique way. Unlike traditional chemotherapy, which attacks rapidly dividing cells in general, brentuximab vedotin is an antibody-drug conjugate that specifically targets CD30, a protein found on the surface of Hodgkin's lymphoma cells. This targeted approach could mean fewer side effects and more effective treatment. Additionally, combining brentuximab vedotin with standard chemotherapy drugs like doxorubicin, vinblastine, and dacarbazine (AVD) might enhance its cancer-fighting abilities, offering new hope for improved outcomes.

What evidence suggests that this treatment might be an effective treatment for Hodgkin's Lymphoma?

Research has shown that combining brentuximab vedotin with the chemotherapy drugs doxorubicin, vinblastine, and dacarbazine (known as BV + AVD) holds promise for treating Hodgkin's lymphoma. Studies indicate that this combination can improve survival rates, particularly for patients with advanced stages of the disease. The ECHELON-1 trial introduced this combination as a new initial treatment and demonstrated its effectiveness against the cancer. Recent data suggests that using brentuximab vedotin with these chemotherapy drugs can yield better results compared to traditional treatments. This trial will further investigate this combination to confirm its benefits for those newly diagnosed with advanced Hodgkin's lymphoma. ^{1 4 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for children with a new diagnosis of advanced stage Hodgkin Lymphoma, specifically stages III and IV. They should have CD30+ classical HL, not have received prior treatment, be relatively active (performance scores >=50), and have measurable disease by certain criteria. Their blood counts and kidney/liver functions must meet the study's standards.

Inclusion Criteria

My Hodgkin's lymphoma is in an advanced stage (Stage III or IV).

My Hodgkin's lymphoma is confirmed to be CD30 positive.

Your disease can be measured and seen on a scan using specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive Brentuximab Vedotin 48 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine to determine the recommended dose

6 months

Days 1 and 15 of each 28-day cycle

Phase 2 Treatment

Participants receive the recommended dose of Brentuximab Vedotin 48 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine

6 months

Days 1 and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 12 weeks for 12 months, then every 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab vedotin
• Dacarbazine
• Doxorubicin
• Vinblastine

Trial Overview The trial is testing Brentuximab Vedotin combined with a chemotherapy regimen including Doxorubicin (Adriamycin), Vinblastine, and Dacarbazine in pediatric patients. It aims to determine the safety, tolerability, proper dosage, and effectiveness against tumors in these young participants.

How Is the Trial Designed?

Group I: Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD Experimental Treatment 4 Interventions

Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.

Group II: Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD Experimental Treatment 4 Interventions

Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.

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?

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

Published Research Related to This Trial

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 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]

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 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]

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, 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8247884/

Brentuximab vedotin plus doxorubicin, vinblastine, and ... Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2531137924025537

Benefits of BV-AVD (Brentuximab vedotin, doxorubicin ... The ECHELON-1 trial introduced brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (BV + AVD) as a novel frontline regimen ...

3. ashpublications.org ashpublications.org/blood/article/145/3/290/526323/Brentuximab-vedotin-nivolumab-doxorubicin-and

Brentuximab vedotin, nivolumab, doxorubicin, and ... ... Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03527628

OPTmizing Advanced Stage HodgkIn LymphoMa patIentS ... This is a prospective, multi-center, open-label, phase II clinical trial, aims to assess the effectiveness of the combination ACVD (Adriamycin, ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/581535

A Study of Brentuximab Vedotin With Doxorubicin, ... The main aim of this study is to check how safe brentuximab vedotin is in adults with untreated Hodgkin Lymphoma (HL) when given together ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03233347

Study Details | NCT03233347 | Doxorubicin, Vinblastine, ... Giving doxorubicin, vinblastine, dacarbazine, brentuximab vedotin, and nivolumab may improve survival of patients with stage I-II Hodgkin lymphoma. Detailed ...

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

Overall Survival with Brentuximab Vedotin in Stage III or IV ... Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39622165/

Brentuximab vedotin, nivolumab, doxorubicin, and ... Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased ...