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

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, 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. Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide chemotherapy regimen may kill more cancer cells.

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 the chemotherapy treatment for Hodgkin's Lymphoma safe?

The chemotherapy treatment, including Brentuximab Vedotin, has been generally well tolerated in trials, with manageable side effects like peripheral neuropathy (nerve damage causing tingling or numbness) and neutropenia (low white blood cell count). Some studies noted hematological toxicities (blood-related side effects) and infections as common adverse events, but these were considered manageable. ^{1 2 3 4 5}

What makes the drug Brentuximab Vedotin combined with Carboplatin, Etoposide, and Ifosfamide unique for treating Hodgkin's Lymphoma?

This drug combination is unique because it includes Brentuximab Vedotin, a targeted therapy that specifically attacks cancer cells expressing CD30, a marker found on Hodgkin lymphoma cells, and is used as a second-line treatment for patients whose disease has relapsed or is resistant to initial therapy. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination including Brentuximab Vedotin for treating Hodgkin's Lymphoma?

Research shows that combining Brentuximab Vedotin with ifosfamide, carboplatin, and etoposide (BV-ICE) as a second-line therapy for relapsed or refractory Hodgkin's Lymphoma resulted in a complete metabolic response in 61.9% of patients after two cycles, with a 3-year progression-free survival rate of 64.3% and overall survival rate of 100%. ^{1 4 6 10 11}

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

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]

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]

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]

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 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 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]

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]

Citations

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

Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. [2022]

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

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study. [2022]

3. United States 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. [2023]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England 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. [2023]

8. England 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. [2019]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Greece pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: first-line agent for advanced Hodgkin lymphoma. [2019]

11. 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]