Mogamulizumab + Brentuximab Vedotin for Mycosis Fungoides

Overseen By Margaret A Thomas, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: CNS involvement, HIV, Hepatitis, 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: Unknown

Duration: 28 days per cycle

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and ideal dosing of a new combination treatment for Mycosis Fungoides, a type of skin lymphoma. Participants will receive Brentuximab Vedotin (an antibody-drug conjugate) and Mogamulizumab (a monoclonal antibody) to evaluate their combined effectiveness. The trial seeks individuals with Mycosis Fungoides or Sézary Syndrome who have CD30 positivity in their biopsy, have previously tried other systemic treatments, and have significant skin involvement. The primary goal is to ensure the treatment combination is safe and to determine a dose for future studies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications, but you must have completed any chemotherapy, radiation, or biologic therapy specific to your condition at least 1 week or 5 half-lives before starting the trial. You also need to be off systemic immunosuppressive medications for at least 30 days if you had a stem cell transplant.

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

Research shows that mogamulizumab is generally well-tolerated by patients with mycosis fungoides, a type of skin cancer. Studies indicate that patients treated with mogamulizumab have a lower risk of needing hospital care and experience fewer serious side effects compared to those treated with brentuximab vedotin.

Mogamulizumab has consistently demonstrated safety in various studies, with many patients experiencing positive results. While brentuximab vedotin is also used in other treatments, it may cause more side effects than mogamulizumab.

In summary, both treatments have been tested for safety, but mogamulizumab usually results in fewer severe side effects than brentuximab vedotin. However, individual experiences can vary, so discussing personal health concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for mycosis fungoides, which often include therapies like phototherapy and systemic retinoids, the combination of Mogamulizumab and Brentuximab Vedotin offers a fresh approach by targeting specific proteins on cancer cells. Mogamulizumab is a monoclonal antibody that targets the CCR4 protein, playing a direct role in the immune system's attack on the cancer cells. Brentuximab Vedotin, on the other hand, is an antibody-drug conjugate that delivers a potent toxin directly to CD30-positive cancer cells, minimizing damage to healthy cells. Researchers are excited about these treatments due to their potential for more precise targeting of cancer cells, possibly leading to greater efficacy and fewer side effects compared to current options.

What evidence suggests that this trial's treatments could be effective for Mycosis Fungoides?

Studies have shown that Brentuximab Vedotin effectively treats certain skin lymphomas, such as Mycosis Fungoides. Research indicates that it significantly aids patients by targeting and destroying cancer cells. Mogamulizumab, another treatment, effectively addresses Mycosis Fungoides and Sézary syndrome by targeting a specific protein on cancer cells. In this trial, participants will receive a combination of these two treatments. Early findings suggest that using Brentuximab Vedotin and Mogamulizumab together might enhance results by attacking cancer cells in different ways. Both treatments have shown promise individually, and their combination could potentially increase effectiveness. ^{3 4 6 7 8}

Who Is on the Research Team?

Amit Mehta, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults over 18 with certain types of skin lymphoma (Sezary Syndrome or Mycosis fungoides) who've had at least one systemic therapy can join. They should have a life expectancy of more than 4 months, no severe chronic diseases, and be able to follow the study plan. Pregnant women, those with recent serious heart issues, uncontrolled infections or diabetes cannot participate.

Inclusion Criteria

My heart's pumping ability is above 40%.

It has been at least 6 months since my transplant.

I am not pregnant or breastfeeding, and I have a negative pregnancy test if applicable.

Exclusion Criteria

Pregnant and lactating women

I have had a solid organ transplant.

Prior severe allergic or anaphylactic reaction to monoclonal antibody or BV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of Mogamulizumab and Brentuximab Vedotin in a dose de-escalation study to assess safety and tolerability

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Mogamulizumab

Trial Overview The trial is testing a combination of two drugs: Brentuximab vedotin and Mogamulizumab for skin lymphomas like CTCL and Mycosis Fungoides. It's an early-phase study focusing on finding the safest dose levels for future research.

How Is the Trial Designed?

Group I: Cohort Experimental Treatment 2 Interventions

Fixed dose of Mogamulizumab and dose de-escalation with Brentuximab Vedotin

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 Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kyowa Kirin China Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

40

Recruited

6,300+

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

Kyowa Kirin, Inc.

Industry Sponsor

Trials

49

Recruited

5,700+

Published Research Related to This Trial

Brentuximab vedotin, an anti-CD30 monoclonal antibody, has shown significant clinical activity in treating advanced mycosis fungoides (MF) and Sezary syndrome, even in cases with low CD30 expression.

A patient with MF and large-cell transformation responded well to brentuximab vedotin, highlighting its potential effectiveness in treatment-refractory cases, although follow-up revealed unusual extensive xanthomatous changes in the biopsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermal xanthomatous infiltrates after brentuximab vedotin therapy in mycosis fungoides with large-cell transformation: A novel histologic finding. Buchely, N., Al-Rohil, RN., Aung, PP., et al.[2019]

Mogamulizumab-kpkc significantly improves progression-free survival in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, showing a PFS of 7.7 months compared to 3.1 months with vorinostat in a phase III trial.

While mogamulizumab-kpkc is effective, it carries risks of serious side effects, including increased risk of severe acute graft-vs.-host disease and other complications, which must be weighed against its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. Watson, S., Marx, JB.[2021]

Mogamulizumab, a novel monoclonal antibody, effectively targets and treats mycosis fungoides and Sèzary syndrome by binding to C-C chemokine receptor 4, enhancing the immune system's ability to attack malignant T-cells.

In a real-life clinical setting in Italy, 12 patients with these skin lymphomas showed significant improvement in symptoms and quality of life when treated with mogamulizumab, indicating its efficacy and manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. Caruso, L., Castellino, A., Dessì, D., et al.[2022]

A patient with a long history of poikilodermatous mycosis fungoides developed CD30-positive large cell transformation after 33 years, indicating a progression of the disease.

The introduction of brentuximab vedotin, a CD30-directed antibody-drug conjugate, resulted in a rapid and excellent therapeutic response after conventional treatments were no longer viable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poikilodermatous mycosis fungoides with CD30-positive large cell transformation successfully treated by brentuximab vedotin. Popadic, S., Lekic, B., Tanasilovic, S., et al.[2020]

Mogamulizumab-kpkc, an FDA-approved treatment for relapsed or refractory mycosis fungoides or Sézary syndrome, significantly improved progression-free survival (PFS) compared to vorinostat, with a median PFS of 7.6 months versus 3.1 months in a study of 372 patients.

While mogamulizumab-kpkc showed a confirmed overall response rate of 28%, it also had notable adverse reactions, including rash and infections, with serious adverse reactions occurring in 36% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sézary Syndrome. Kasamon, YL., Chen, H., de Claro, RA., et al.[2020]

Mogamulizumab shows promising efficacy for patients with advanced cutaneous T-cell lymphomas, with a median progression-free survival (PFS) of 22 months based on a study of 21 patients followed for an average of 11.6 months.

The safety profile of mogamulizumab is considered acceptable, with 20 patients experiencing adverse events, of which only 10 were severe (grade III-IV), and the median time to the first adverse event was 21 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. Jouandet, M., Nakouri, I., Nadin, L., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9095533/

Mogamulizumab for Previously Treated Mycosis Fungoides ... Mogamulizumab for previously treated Mycosis Fungoides and Sézary syndrome: an evidence review group perspective of a NICE single technology appraisal.

2. jidonline.org jidonline.org/article/S0022-202X(25)01919-0/pdf

LB1078 Our data suggest a reduced risk of hospitalization and serious adverse events in MF/SS patients treated with mogamulizumab compared to brentuximab vedotin, ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602684/

Clinical Review - Mogamulizumab (Poteligeo) - NCBI - NIH The objective of the current review is to review the beneficial and harmful effects of mogamulizumab 1.0 mg/kg for the treatment of adults with relapsed or ...

4. everyone.org everyone.org/explore/compare?id1=120&id2=167

Adcetris (brentuximab vedotin) vs Poteligeo ... Poteligeo (mogamulizumab) is a monoclonal antibody that targets CCR4, used for the treatment of mycosis fungoides and Sézary syndrome, which are types of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804923006457

EORTC consensus recommendations for the treatment of ... The safety and efficacy of brentuximab vedotin in CTCL was shown in an international, open-label, randomised, phase 3, multicentre trial (ALCANZA) [161]. Ninety ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05414500

Mogamulizumab and Brentuximab Vedotin in CTCL ... This is an open label, single center, non-randomized dose de-escalation phase I study of combination of BV and Mogamulizumab.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7517756/

Mogamulizumab-kpkc: A Novel Therapy for the Treatment ... Mogamulizumab-kpkc provides a novel mechanism of action for the treatment of mycosis fungoides and Sézary syndrome. The efficacy and safety of mogamulizumab- ...

8. lymphomahub.com lymphomahub.com/medical-information/the-efficacy-and-safety-of-mogamulizumab-for-advanced-mycosis-fungoides-and-sezary-syndrome

The efficacy and safety of mogamulizumab for advanced ... The antibody was most active in patients with advanced disease and resulted in responses of 36% in those with MF, and 37% in patients with SS.