Chemotherapy for Hodgkin's Lymphoma

(BV-ICE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must not be taking: Brentuximab vedotin

Disqualifiers: HIV, Pregnancy, CNS lymphoma, 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: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose and examine the effects of a new drug combination for Hodgkin's lymphoma, specifically targeting cases where cancer has returned or resisted existing treatments. It tests a mix of brentuximab vedotin, which targets cancer cells, alongside chemotherapy drugs like ifosfamide, carboplatin, and etoposide, which aim to halt cancer cell growth and spread. Individuals with relapsed or treatment-resistant Hodgkin's lymphoma may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects in people and assessing its effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in Hodgkin's lymphoma treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot use other anti-cancer agents or experimental treatments while participating.

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

Studies have shown that combining brentuximab vedotin with the chemotherapy drugs ifosfamide, carboplatin, and etoposide is generally well-tolerated. Past research used this combination to treat patients with Hodgkin lymphoma that had returned or did not respond to previous treatments. Evidence suggests that most patients managed the treatment without serious side effects. While some experienced issues like low blood cell counts and infections, these are common with chemotherapy.

Brentuximab vedotin is already approved for other uses, indicating its general safety. This trial tests its use with other chemotherapy drugs to help people with hard-to-treat Hodgkin lymphoma. As with any clinical trial, risks exist, but earlier studies have shown this combination to be relatively well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Hodgkin's Lymphoma because they bring a fresh approach to tackling the disease. Brentuximab vedotin is a targeted therapy that zeroes in on CD30, a protein found on Hodgkin's Lymphoma cells, delivering a potent anti-cancer drug directly to the tumor. This targeted action is different from traditional chemotherapy, which affects both healthy and cancerous cells. Additionally, the combination of brentuximab with carboplatin, etoposide, and ifosfamide brings together powerful agents that may enhance effectiveness and potentially reduce side effects compared to standard regimens. These treatments are paving the way for potentially more effective and tailored therapies.

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

Research has shown that combining the drug brentuximab vedotin with ifosfamide, carboplatin, and etoposide may effectively treat Hodgkin lymphoma that has returned or is resistant to other treatments. In this trial, participants will receive varying doses of brentuximab vedotin along with ifosfamide, carboplatin, and etoposide. Studies have found that this combination can successfully attack and destroy cancer cells. Specifically, a previous study demonstrated that many patients experienced a reduction or disappearance of their cancer, known as a partial or complete response. These findings suggest that this therapy could be a strong option for those whose lymphoma has returned or is unresponsive to other treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with Hodgkin lymphoma that hasn't responded to initial treatment or has returned. They must have a certain level of blood cells, organ function, and be able to complete two chemotherapy cycles. Pregnant individuals, those with HIV or other recent cancers (except some skin and in situ cancers), allergies to specific drugs used here, active central nervous system lymphoma, prior brentuximab vedotin use, significant neuropathy or heart issues are excluded.

Inclusion Criteria

I have a tumor that can be seen on scans or felt and is confirmed by a PET scan.

Aspartate aminotransferase (AST) < 2.5 times upper limit of normal, performed within 28 days prior to registration

All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines

Exclusion Criteria

I have previously received brentuximab vedotin treatment.

I haven't had chemotherapy or immunotherapy in the last 3 weeks.

Concurrent use of other anti-cancer agents or experimental treatments

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin, ifosfamide, carboplatin, and etoposide chemotherapy regimen

6 weeks

2 courses, each 21 days apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

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

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Carboplatin
• Etoposide
• Ifosfamide

Trial Overview

The study is testing the combination of brentuximab vedotin (a targeted cancer drug) with ifosfamide, carboplatin, and etoposide (chemotherapy drugs). It aims to find the safest dose of brentuximab vedotin that can be given alongside these chemotherapies to treat relapsed/refractory Hodgkin lymphoma more effectively.

How Is the Trial Designed?

Group I: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide) Experimental Treatment 5 Interventions

Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

Group II: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide) Experimental Treatment 5 Interventions

Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

Group III: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide) Experimental Treatment 5 Interventions

Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

The combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) was found to be safe and effective as a second-line therapy for patients with refractory/relapsed classical Hodgkin lymphoma, with 61.9% achieving a complete metabolic response after 2 cycles.

With a median follow-up of 38 months, the treatment showed promising long-term outcomes, including a 3-year progression-free survival rate of 64.3% and an overall survival rate of 100%, indicating its potential as a viable alternative to other salvage therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study. Stamatoullas, A., Ghesquières, H., Feugier, P., et al.[2023]

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]

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 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 clinically meaningful response in 47% of pediatric patients with relapsed or refractory classical Hodgkin's lymphoma and 53% for systemic anaplastic large-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being pyrexia and nausea, and 44% of patients experiencing at least one grade 3 or worse adverse event, suggesting that while side effects occurred, they were generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Locatelli, F., Mauz-Koerholz, C., Neville, K., et al.[2019]

In a study of 1334 patients with untreated stage III or IV Hodgkin's lymphoma, those treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) showed a significant overall survival advantage compared to those receiving the standard ABVD regimen, with a 6-year survival rate of 93.9% versus 89.4%.

A+AVD also resulted in longer progression-free survival and fewer patients requiring subsequent therapies, although it was associated with a higher incidence of peripheral neuropathy, which mostly resolved by the last follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. Ansell, SM., Radford, J., Connors, JM., et al.[2022]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35975738/

Final results of brentuximab vedotin combined with ...

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/ ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02227199?tab=results

Study Results | NCT02227199 | Brentuximab Vedotin, ...

Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and ...

3.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/3043/532756/Dose-Dense-Brentuximab-Vedotin-Plus-Ifosfamide

Dose-Dense Brentuximab Vedotin Plus Ifosfamide ...

Dose-dense Brentuximab Vedotin Plus Ifosfamide, carboplatin, and etoposide (ICE) in second line treatment of relapsed/refractory classical hodgkin lymphoma.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124057951

Dose-Dense Brentuximab Vedotin Plus Ifosfamide, ...

Background: Classical Hodgkin lymphoma (CHL) patients (pts) requiring second line therapy may still be cured with multiagent salvage ...

5.

thelancet.com

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Dose-dense brentuximab vedotin plus ifosfamide ...

The aim of this study is to establish the safety and activity of dose-dense brentuximab vedotin combined with ifosfamide, carboplatin, and etoposide (BV-ICE) ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34329577/

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin ...

The aim of this study is to establish the safety and activity of dose-dense brentuximab vedotin combined with ifosfamide, carboplatin, and etoposide (BV-ICE) ...

7.

ohsu.edu

ohsu.edu/sites/default/files/2025-08/HS-MPS-Adcetris-E.06.25.pdf

Adcetris® (brentuximab vedotin)

Adult cHL in combination with ifosfamide, carboplatin, and etoposide (ICE) has a maximum of 4 doses. • Adult cHL in combination with etoposide, cyclophosphamide ...

8.

ashpublications.org

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In patients with relapsed disease, the BV cohort showed a significantly better 3-year PFS than the chemotherapy cohort of 79.9% (95% CI, 74-87) vs 69.7% (95% ...