Brentuximab Vedotin for Cutaneous T-Cell Lymphoma

Recruiting at 7 trial locations

Overseen by Alison Moskowitz, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic anti-cancer agents

Disqualifiers: Neuropathy, Renal impairment, Hepatic impairment, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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 Brentuximab Vedotin safe for humans?

Brentuximab Vedotin has been studied in several trials for cutaneous T-cell lymphoma, showing it is generally safe for humans, but like many treatments, it can have side effects. Common side effects include low blood cell counts, nerve damage, and fatigue, so it's important to discuss these with your doctor. ^{1 2 3 4 5}

How is the drug Brentuximab Vedotin different from other treatments for cutaneous T-cell lymphoma?

Brentuximab Vedotin is unique because it is a targeted therapy that specifically binds to CD30 receptors on cancer cells, delivering a potent cell-killing agent directly to the tumor, which can lead to better response rates and longer progression-free survival compared to conventional treatments. ^{1 2 3 4 5}

Research Team

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Inclusion Criteria

Mycosis fungoides (MF) and Sezary Syndrome (SS): Pathologically confirmed mycosis fungoides/sezary syndrome at the enrolling institution, disease stage IB or higher, CD30 negative mycosis fungoides patients eligible, Age ≥ 18 years, ECOG Performance Score ≤ 2, Previous systemic anti-cancer therapy discontinued at least 2 weeks prior to treatment, Topical or systemic steroids may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, If HIV+, stable anti-retroviral treatment for 12 weeks prior to C1D1, CD4 count >200 within 7 days prior to C1D1, Females of childbearing potential on acceptable form of birth control per institutional standard

Lymphomatoid papulosis (LyP): Pathologically confirmed lymphomatoid papulosis at the enrolling institution, Requiring systemic treatment per investigator's discretion, Age ≥ 18 years, ECOG Performance Score ≤ 2, Previous systemic anti-cancer therapy discontinued at least 2 weeks prior to treatment, Topical or systemic steroids may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, If HIV+, stable anti-retroviral treatment for 12 weeks prior to C1D1, CD4 count >200 within 7 days prior to C1D1, Females of childbearing potential on acceptable form of birth control per institutional standard

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

Trial Timeline

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

Treatment Details

Interventions

• Brentuximab Vedotin (Monoclonal Antibodies)

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.

Participant Groups

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.

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

Findings from Research

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]

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 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 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 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]

References

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

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. [2019]

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

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. [2021]

3. England 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. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry. [2022]

5. England 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. [2020]