Brentuximab + AVD Chemotherapy for Hodgkin's Lymphoma

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic steroids

Disqualifiers: HIV/AIDS, Pregnancy, Cardiac issues, 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: 8

Duration: 16 weeks

118 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 it does mention that patients on chronic steroid treatment are excluded, except for those who have taken steroids for up to 10 days before starting the trial treatment.

What data supports the effectiveness of the drug Brentuximab vedotin (SGN-35) combined with AVD chemotherapy for treating Hodgkin's Lymphoma?

Research shows that Brentuximab vedotin combined with AVD chemotherapy is effective in reducing the risk of disease progression in advanced stage Hodgkin lymphoma compared to standard treatments. It has also shown promising results in patients with relapsed or heavily treated Hodgkin lymphoma. ^{1 2 3 4 5}

Is the combination of Brentuximab vedotin with AVD chemotherapy safe for treating Hodgkin's Lymphoma?

The combination of Brentuximab vedotin with AVD chemotherapy has been studied for safety in treating Hodgkin's Lymphoma. Common side effects include nerve damage (peripheral sensory neuropathy), low white blood cell counts (neutropenia), tiredness (fatigue), and nausea. Serious side effects can occur, such as severe neutropenia and infections, and dose adjustments may be needed for some patients. ^{1 2 3 4 6}

How is the drug Brentuximab vedotin with AVD different from other treatments for Hodgkin's Lymphoma?

Brentuximab vedotin with AVD is unique because it replaces bleomycin with brentuximab vedotin, an antibody-drug conjugate that targets CD30, a protein found on Hodgkin lymphoma cells, which has shown to improve progression-free survival in advanced stages compared to the standard ABVD regimen. ^{1 2 3 5 7}

What is the purpose of this trial?

The purpose of this study is to compare the outcomes across the 4 different treatment groups. The investigators hope that this treatment will improve the ability to cure more patients with HL and also limit the long-term side effects from the treatment. Although eliminating radiation in cohort 4 will eliminate the risk for long-term side effects from radiation, it is also possible that with BV+AVD chemotherapy alone there may be an increased risk of the Hodgkin lymphoma coming back after initial treatment.

Research Team

Anita J Kumar

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with early stage, high-risk Hodgkin lymphoma. Participants must have FDG-avid and measurable disease, a specific size of lymph node mass, and agree to birth control if applicable. Excluded are those with certain blood counts, liver or kidney issues, pregnant or breastfeeding women, HIV/AIDS patients, individuals with peripheral neuropathy or on long-term steroids.

Inclusion Criteria

Females of childbearing age must be on an acceptable form of birth control per institutional standards

I have a lymph node mass larger than 7.0 cm.

My cancer is in the early stages (Stage I or II).

Exclusion Criteria

Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

My heart's pumping ability is reduced.

My nerve damage does not severely affect my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 cycles of brentuximab vedotin and AVD chemotherapy. Brentuximab vedotin is administered on days 1 and 15 of each 28-day cycle, along with Doxorubicin, Vinblastine, and Dacarbazine.

16 weeks

8 visits (in-person)

Radiotherapy

Participants may receive involved site radiotherapy, with doses varying by cohort (20 Gy to 30.6 Gy).

2-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of PET-negative complete responses.

1 year

Treatment Details

Interventions

• Brentuximab vedotin (SGN-35)
• Consolidation Volume RT (CVRT)
• Dacarbazine
• Doxorubicin HCL
• Involved-Site Radiation Therapy (ISRT)
• Vinblastine Sulfate

Trial Overview The study tests Brentuximab Vedotin combined with AVD chemotherapy against three other treatment groups involving radiation therapy and interim PET scans. The goal is to cure more patients while reducing long-term side effects from treatments.

Participant Groups

Group I: Cohort 4 Experimental Treatment 5 Interventions

Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter \> 7.0 cm or coronal maximal diameter \> 7.0 cm. In this cohort. Pts will receive 4 cycles of brentuximab vedotin \& AVD chemo. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 \& 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, \& Dacarbazine 375 mg/m2 will be administered on days 1 \& 15 of each 28 day cycle. Pts whose PET scan is negative after 4 cycles of brentuximab vedotin \& AVD chemotherapy will not receive RT. Pts whose PET scan is positive after 4 cycles of brentuximab vedotin \& AVD chemo, but subsequent biopsy is neg, will also receive no RT. Upon MSK PI approval, if the simulation can't be covered by the institution or the pts insurance, a diagnostic IV contrast CT neck \& diagnostic IV contrast CT CAP scan will be done in addition to the FDG-PET done after 4 cycles of chemo.

Group II: Cohort 3 Experimental Treatment 6 Interventions

Patients will have early stage, unfavorable risk classical Hodgkin lymphoma with disease bulk defined as the presence of any lymph node mass with transverse maximal diameter \> 7.0 cm or coronal maximal diameter \> 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin and AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30.6 Gy CVRT.

Group III: Cohort 2 Experimental Treatment 6 Interventions

Patients with early stage, unfavorable risk Hodgkin lymphoma. The definition of disease bulk, one of the unfavorable risk features, has been updated, and is defined as the presence of any lymph node mass with transverse maximal diameter \> 7.0 cm OR coronal maximal diameter \> 7.0 cm. Patients will receive 4 cycles of brentuximab vedotin \& AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, and Dacarbazine 375 mg/m2 will be administered on days 1 \& 15 of each 28 day cycle. This may be followed by 20 Gy involved site radiotherapy.

Group IV: Cohort 1 (completed accrual) Experimental Treatment 6 Interventions

Patients received 4 cycles of brentuximab vedotin \& AVD chemotherapy. Brentuximab vedotin, 1.2 mg/kg, will be administered on days 1 and 15 of each 28 day cycle. Doxorubicin 25 mg/m2, Vinblastine 6 mg/m2, \& Dacarbazine 375 mg/m2 will be administered on days 1 and 15 of each 28 day cycle. This may be followed by 30 Gy involved site radiotherapy. Involved site radiotherapy should be initiated from 12 days to 42 days after completion of chemotherapy. It is mandatory to administer prophylactic growth factor support starting with cycle 1. Choice of growth factor and dosing can be determined at the discretion of the treating physican.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Findings from Research

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]

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]

Brentuximab vedotin (BV) combined with doxorubicin, vinblastine, and dacarbazine (AVD+BV) improves clinical outcomes in adults with stage III or IV Hodgkin lymphoma, providing an increase of 0.56 quality-adjusted life-years (QALYs) compared to standard ABVD therapy.

However, the use of BV significantly raises lifetime healthcare costs, resulting in an incremental cost-effectiveness ratio (ICER) of $317,254 per QALY, indicating that it is unlikely to be cost-effective at current pricing without substantial price reductions for BV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma. Huntington, SF., von Keudell, G., Davidoff, AJ., et al.[2019]

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 the ECHELON-1 study involving 1334 patients with stage III or IV classical Hodgkin lymphoma, the A+AVD treatment (brentuximab vedotin combined with standard chemotherapy) demonstrated a significantly better 5-year progression-free survival rate of 82.2% compared to 75.3% for the ABVD treatment, indicating its superior efficacy.

The safety profile of A+AVD was consistent, with fewer secondary malignancies reported compared to ABVD, and while more patients experienced ongoing peripheral neuropathy with A+AVD, the condition improved over time, suggesting a manageable side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Straus, DJ., Długosz-Danecka, M., Connors, JM., et al.[2022]

References

1. 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]

2. 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]

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. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin for relapsed or refractory CD30+ Hodgkin lymphoma: a multicenter analysis from Asia. [2021]

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

Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma. [2019]

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

Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. [2022]