Mogamulizumab + Brentuximab Vedotin for Mycosis Fungoides

Overseen By Mona Collins

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: CNS involvement, HIV, Hepatitis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is an open label, single center, non-randomized dose de-escalation phase I study of combination of BV and Mogamulizumab. The primary objective of the study is to assess the safety and tolerability of the combination. The primary objective is also to explore safe dose of combination for future expansion.

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.

What data supports the effectiveness of the drug combination Mogamulizumab and Brentuximab Vedotin for treating Mycosis Fungoides?

Brentuximab Vedotin has shown effectiveness in treating CD30-positive cutaneous T-cell lymphomas, including Mycosis Fungoides, by targeting specific cancer cells. Mogamulizumab has been effective in controlling cutaneous T-cell lymphomas, improving symptoms and quality of life in patients with Mycosis Fungoides and Sézary syndrome. Together, these drugs target different aspects of the disease, potentially offering a comprehensive treatment approach. ^{1 2 3 4 5}

What safety data exists for Mogamulizumab and Brentuximab Vedotin in humans?

Mogamulizumab has been associated with side effects like rash, fatigue, diarrhea, and infections, with serious reactions occurring in 36% of patients, often due to infections. Brentuximab Vedotin has been used safely in patients with CD30-positive lymphomas, but specific safety data from trials is not detailed in the provided articles. ^{1 2 4 6 7}

What makes the drug combination of Mogamulizumab and Brentuximab Vedotin unique for treating mycosis fungoides?

This drug combination is unique because Mogamulizumab targets the CCR4 receptor on cancer cells, enhancing the immune system's ability to attack them, while Brentuximab Vedotin targets CD30+ receptors, delivering a potent toxin directly to the cancer cells. This dual approach may offer a more effective treatment option for patients with advanced mycosis fungoides compared to existing therapies. ^{1 3 4 6 7}

Research Team

Amit Mehta, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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 over 18 and have been diagnosed with Sezary Syndrome or Mycosis fungoides.

Exclusion Criteria

Pregnant and lactating women

I have had a solid organ transplant.

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

Trial Timeline

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

Treatment Details

Interventions

• Brentuximab Vedotin (Monoclonal Antibodies)
• Mogamulizumab (Monoclonal Antibodies)

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.

Participant Groups

Group I: Cohort Experimental Treatment 2 Interventions

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

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+

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]

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 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, 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-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]

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

Poikilodermatous mycosis fungoides with CD30-positive large cell transformation successfully treated by brentuximab vedotin. [2020]

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

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. [2022]

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

Dermal xanthomatous infiltrates after brentuximab vedotin therapy in mycosis fungoides with large-cell transformation: A novel histologic finding. [2019]

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

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. [2021]

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

FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sézary Syndrome. [2020]