Brentuximab Vedotin for Cutaneous T-Cell Lymphoma

Recruiting at 7 trial locations

Overseen By Alison Moskowitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic anti-cancer agents

Disqualifiers: Neuropathy, Renal impairment, Hepatic impairment, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 1 year

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a lower dose of the drug brentuximab vedotin affects individuals with certain skin-related lymphomas. It focuses on treating cutaneous T-cell lymphoma, specifically mycosis fungoides, Sezary syndrome, and lymphomatoid papulosis. The trial aims to understand the benefits and side effects of this treatment at reduced doses. It suits individuals diagnosed with these conditions who have noticeable skin symptoms. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking any systemic anti-cancer medications at least 2 weeks before starting the trial. However, if you are on a stable dose of topical or systemic steroids, you might be able to continue them after discussing with the study doctor. If you are HIV positive, you must be on stable anti-retroviral treatment for at least 12 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that brentuximab vedotin is generally well-tolerated by individuals with certain skin-related lymphomas, such as cutaneous T-cell lymphoma and lymphomatoid papulosis. One study found that about 73% of patients responded positively to the treatment, suggesting that most people manage it well. While side effects have been reported, they are common with many cancer treatments. This trial tests a lower dose of brentuximab vedotin than the FDA typically approves, which might reduce the risk or intensity of side effects. Discussing any concerns about treatment safety with a doctor is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Cutaneous T-Cell Lymphoma (CTCL), which often include therapies like corticosteroids, chemotherapy, or phototherapy, Brentuximab Vedotin offers a targeted approach by delivering a chemotherapy drug directly to cancer cells. This is achieved through an antibody-drug conjugate mechanism, which specifically targets the CD30 protein found on some lymphoma cells. Researchers are excited about Brentuximab Vedotin because this targeted delivery method can potentially reduce damage to healthy cells, leading to fewer side effects and improved effectiveness. Moreover, it offers a new option for patients who have already undergone other treatments, providing hope for those with limited options.

What evidence suggests that brentuximab vedotin might be an effective treatment for cutaneous T-cell lymphoma?

Research has shown that brentuximab vedotin effectively treats cutaneous T-cell lymphoma (CTCL), particularly in patients whose tumors express the CD30 protein. Studies have found that it can yield positive results, even in advanced stages, with manageable side effects. In this trial, participants will receive varying doses of brentuximab vedotin based on their previous treatment history. Specifically, one study found that patients taking brentuximab vedotin responded significantly better than those receiving standard treatments like methotrexate or bexarotene. This drug targets cancer cells directly, helping to kill them while causing less harm to normal cells. Overall, the evidence supports its effectiveness in improving outcomes for patients with CD30-positive CTCL. ^{2 4 6 7 8}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with Mycosis Fungoides or Sezary Syndrome who need treatment can join this trial. It's for those who haven't tried Brentuximab Vedotin, or have used it before without success. People must be generally healthy and not pregnant, with no severe kidney, liver issues, or neuropathy. They should not be on other cancer treatments.

Exclusion Criteria

Concurrent use of other systemic anti-cancer agents or treatments for mycosis fungoides/sezary syndrome, or lymphomatoid papulosis, Grade 2 or greater neuropathy, Severe renal impairment (CrCL <30 mL/min), Moderate or severe hepatic impairment (Child-Pugh B or Child-Pugh C), Women of reproductive potential must have a negative Serum ß human chorionic gonadotropin (ß-HCG) pregnancy test within 1 week of C1D1, Previous use of brentuximab vedotin (for Cohort 1 ONLY), Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma), Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator, Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) permissible after discussion with the MSK Principal Investigator, For Cohort 2, patients who previously progressed on the standard 1.8mg/kg dose and schedule of brentuximab vedotin are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive brentuximab vedotin at a reduced dose, with different cohorts receiving different dosages. Treatment is administered every three weeks.

Up to 1 year

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with overall response measured by the global response score.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin

Trial Overview The trial is testing a lower dose of Brentuximab Vedotin than the usual FDA-approved amount to see if it's effective and has fewer side effects for skin lymphoma conditions like Mycosis Fungoides and Sezary Syndrome.

How Is the Trial Designed?

Group I: treated with reduced dose brentuximab vedotin Experimental Treatment 1 Intervention

Patients with MF/SS who were previously treated with brentuximab vedotin. Up to 10 patients will be enrolled onto this cohort. Following identification of a promising dose after the completion of the full Cohort 1 Simon two stage design, enrollment will initiate onto cohort 2 at the dose found to be promising in cohort 1. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. The 0.9mg/kg dose did not meet the primary endpoint for response, therefore 1.2 mg/kg has been chosen as the dose for Cohort 2. As of October 2020, enrollment on our exploratory Cohort 2 has opened at the 1.2 mg/kg dose.

Group II: not been previously treated with brentuximab vedotin. Experimental Treatment 1 Intervention

Patients with MF/SS who have not been previously treated with brentuximab vedotin. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. As of October 2020, the Simon two stage design for Cohort 1 has restarted at the 1.2 mg/kg dose.

Group III: Patients with LyP Experimental Treatment 1 Intervention

Patients with LyP patients with lymphomatoid papulosis will receive brentuximab vedotin 0.9 mg/kg as an intravenous infusion over 30 minutes every three weeks. Cohort 3 will enroll patients concurrently with Cohort 1. Treatment may be held if felt to be in patient's best interest (for example: for toxicity or no active disease). Treatment can be reinitiated after discussion with MSK PI as long as the study is still open and patient has not received alternate systemic therapy.

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?

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

Published Research Related to This Trial

In a phase 3 trial involving 131 patients with CD30-positive cutaneous T-cell lymphomas, brentuximab vedotin demonstrated a significantly higher objective response rate lasting at least 4 months (56.3%) compared to conventional therapies (12.5%), indicating its superior efficacy.

While brentuximab vedotin was associated with a higher incidence of peripheral neuropathy (67% of patients), the overall safety profile was comparable to conventional therapies, with similar rates of grade 3-4 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Prince, HM., Kim, YH., Horwitz, SM., et al.[2019]

In a retrospective case series of 13 patients with Sézary syndrome, brentuximab vedotin demonstrated a global response rate of 38%, with notable efficacy in blood (63% response) and lymph nodes (50% response), suggesting it may be a viable treatment option for this challenging condition.

The treatment was generally well-tolerated, with manageable side effects such as peripheral neuropathy, which resolved in some cases, indicating that brentuximab vedotin could provide a safer alternative for patients with refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. Lewis, DJ., Haun, PL., Samimi, SS., et al.[2021]

In a study of 67 patients with cutaneous T-cell lymphoma (CTCL), brentuximab vedotin (BV) demonstrated a 67% overall response rate, with particularly high efficacy in patients with CD30+ lymphoproliferative disorders (84%) and folliculotropic mycosis fungoides (71%).

The treatment was generally well-tolerated, with the most common side effect being peripheral neuropathy, which was mostly mild (grades 1 or 2) in 57% of patients, indicating that BV is both effective and relatively safe for advanced-stage CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry. Muniesa, C., Gallardo, F., García-Doval, I., et al.[2022]

Brentuximab vedotin demonstrated a high overall response rate of 73% and a complete response rate of 35% in 48 patients with CD30(+) cutaneous T-cell lymphomas, indicating its efficacy as a treatment option.

The treatment was generally well tolerated, with most adverse effects being grade 1 to 2 peripheral neuropathy observed in 65% of patients, while serious side effects were relatively rare, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. Duvic, M., Tetzlaff, MT., Gangar, P., et al.[2019]

Brentuximab vedotin significantly reduced symptom burden in patients with CD30-expressing cutaneous T-cell lymphoma compared to physician's choice treatments, with a mean maximum reduction in symptom scores of -27.96 versus -8.62, exceeding the minimally important difference.

Quality of life measures, including FACT-G and EQ-5D scores, remained comparable between brentuximab vedotin and physician's choice, indicating that the treatment did not adversely affect patients' overall well-being, even in those experiencing peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Dummer, R., Prince, HM., Whittaker, S., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36017748/

Brentuximab vedotin in the treatment of cutaneous T-cell ... Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment.

2. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(23)02146-8/fulltext

Real-World Treatment Patterns and Clinical Outcomes With ... This retrospective chart review describes patient characteristics, treatment patterns, clinical outcomes, and healthcare resource use (HRU) in patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01578499

NCT01578499 | A Phase 3 Trial of Brentuximab Vedotin ... This study will look at the overall response of people who took brentuximab vedotin compared to people who took methotrexate or bexarotene as standard care.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/dth/7123954

Clinical Experience With Brentuximab Vedotin in Treating ... BV, either as monotherapy or combined with chemotherapy, showed a good response in the treatment of advanced CTCL patients with good tolerability.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2473952921005322

Randomized phase 3 ALCANZA study of brentuximab ... The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4737859/

Results of a Phase II Trial of Brentuximab Vedotin ... Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03587844

Dosing of Brentuximab Vedotin for Mycosis Fungoides ... The purpose of this study is to test any good and bad effects of the study drug called brentuximab vedotin at a lower dose than is FDA-approved. Official Title.

8. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(17)31266-7/abstract

Brentuximab vedotin or physician's choice in CD30 ... We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell ...