Photopheresis + Mogamulizumab for Cutaneous T-Cell Lymphoma

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Prior mogamulizumab, Active infection, Autoimmune disorders, 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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments for a rare type of skin cancer called cutaneous T-cell lymphoma (CTCL). The treatments include extracorporeal photopheresis (ECP), which treats blood with ultraviolet light, and mogamulizumab, a drug that may stop cancer cells from growing. The goal is to determine if these treatments together can more effectively fight the cancer and enhance the immune system's response. Individuals with CTCL who have a widespread red rash and have not received certain prior treatments might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy, including monoclonal antibodies, chemotherapy, radiation, biological therapy, or immunotherapy, at least 21 days before starting the study. Additionally, you must stop any skin-directed therapy 14 days before starting the trial. However, certain medications like low-dose systemic corticosteroids and stable doses of prophylactic antibiotics for staphylococcus colonization are allowed.

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

Previous studies have shown that extracorporeal photopheresis (ECP) is a safe treatment for patients with cutaneous T-cell lymphoma (CTCL). Reports indicate no severe (grade 3 or 4) ECP-related side effects, suggesting ECP is generally well-tolerated and reliable for treating CTCL.

Research on mogamulizumab shows it helps control the disease in CTCL patients. Although it can cause side effects, the treatment has demonstrated significant benefits in extending the lives of patients with advanced CTCL. The safety profile is acceptable, but, like many cancer treatments, some side effects may occur.

Both treatments have promising safety records, suggesting they might work well together for CTCL treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining mogamulizumab with extracorporeal photopheresis (ECP) for treating cutaneous T-cell lymphoma because these treatments offer a unique approach. Mogamulizumab is a monoclonal antibody that specifically targets the CCR4 protein on cancer cells, a mechanism not utilized by standard therapies like chemotherapy or radiation. Additionally, ECP is an innovative technique that involves treating blood outside the body to enhance the immune response against cancer cells, offering a different angle compared to traditional treatments. This combination has the potential to provide more effective and targeted treatment options for patients with this condition.

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

Research has shown that extracorporeal photopheresis (ECP) can effectively treat cutaneous T-cell lymphoma (CTCL). Studies indicate that ECP leads to improvement in 31-86% of patients, depending on various factors. Additionally, some patients have experienced long-lasting remission with ECP.

In this trial, participants will receive both ECP and mogamulizumab. Clinical trials have demonstrated that mogamulizumab effectively targets certain cancer cells, resulting in tumor shrinkage. Specifically, one important study found that 49.2% of patients treated with mogamulizumab had lasting improvements in their blood, and 27.4% had improvements in their skin. Together, these treatments may offer a promising way to manage CTCL. ^{1 6 7 8 9}

Who Is on the Research Team?

Christiane Querfeld, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults (18+) with erythrodermic cutaneous T cell lymphoma, specifically mycosis fungoides or Sezary syndrome. Participants must have an ECOG performance status of <=2, meet certain blood and organ function criteria, agree to birth control if applicable, and can provide tissue samples. Excluded are those who've had recent cancer treatments or live vaccines, other active malignancies within 5 years (with some exceptions), unstable heart disease, autoimmune disorders in the past 3 years (with exceptions), infections needing systemic treatment, or require dialysis.

Inclusion Criteria

Assent, when appropriate, will be obtained per institutional guideline

Documented informed consent of the participant and/or legally authorized representative

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

I do not have any other active cancer.

I require dialysis for kidney failure.

I have had a stem cell transplant before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mogamulizumab IV and undergo ECP. Treatment repeats every 28 days for up to 6 cycles.

24 weeks

4 visits per cycle (in-person)

Extended Treatment

Participants achieving CR/PR after 6 cycles receive up to 6 additional cycles of treatment.

24 weeks

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Extracorporeal Photopheresis
• Mogamulizumab

Trial Overview The trial is testing a combination therapy for skin lymphoma involving extracorporeal photopheresis—where white blood cells are treated with UV light outside the body—and mogamulizumab—a monoclonal antibody that may stop cancer growth. The study aims to see if this combo can effectively kill tumor cells and boost immune response against cancer.

How Is the Trial Designed?

Group I: Treatment (ECP, mogamulizumab) Experimental Treatment 4 Interventions

Patients receive mogamulizumab IV over 60 minutes on days 1, 8, 15, 22, of cycle 1 and days 1 and 15 of subsequent cycles. Beginning in cycle 2, patients also undergo ECP over 3 hours on days 8, 9, 22,and 23. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CR)/PR after 6 cycles receive up to 6 additional cycles of treatment in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Photopheresis is an effective treatment for advanced cutaneous T-cell lymphoma, especially in cases of Sezary syndrome, and may also benefit certain autoimmune diseases and organ transplant rejection.

This therapy is very well tolerated by patients and does not appear to have direct immunosuppressive effects, suggesting it could be a safe option for various conditions, warranting further randomized trials to explore its full potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of photopheresis. Rook, AH., Cohen, JH., Lessin, SR., et al.[2007]

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]

Extracorporeal photopheresis (ECP) was effective in treating leukemic cutaneous T-cell lymphoma (L-CTCL), with 12 out of 18 patients showing clinical responses after therapy, indicating its potential as a viable treatment option.

The study found that responders had significantly higher levels of regulatory T cells (CD4(+) Foxp3(+) T cells) compared to nonresponders, suggesting that these cells may play a role in the treatment's efficacy and could help in monitoring patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD4(+) Foxp3(+) CD25(-) T cells in patients with leukemic cutaneous T-cell lymphoma. Shiue, LH., Couturier, J., Lewis, DE., et al.[2018]

In a study of 13 patients with cutaneous T-cell lymphoma (CTCL), mogamulizumab treatment led to significant reductions in T cells, with a 57% decrease in total CD3+ T cells and up to 75% in aberrant T cell populations after four treatment cycles.

The reduction in aberrant T cells was noticeable after just one dose of mogamulizumab, indicating its potential effectiveness, although no clear correlation was found between the decrease in aberrant T cells and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis. Gosmann, J., Bielefeld, A., Schmitz, FJ., et al.[2023]

Mogamulizumab, an anti-CC chemokine receptor 4 monoclonal antibody, showed a favorable safety profile in a phase 1/2 study with 41 patients, as no dose-limiting toxicity was observed and most adverse events were mild (grade 1/2).

The treatment demonstrated an overall response rate of 36.8% in patients with cutaneous T-cell lymphoma, with particularly high efficacy (47.1%) in those with Sézary syndrome, suggesting that further phase 3 studies are justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Duvic, M., Pinter-Brown, LC., Foss, FM., et al.[2021]

In a study of 41 patients with advanced cutaneous T-cell lymphoma (CTCL), extracorporeal photopheresis showed a high response rate, with 25% achieving complete remission and 46% achieving partial remission after six or more treatment cycles.

Combining photopheresis with interferon alfa resulted in enhanced clinical responses for some patients, and this combination therapy was well tolerated, suggesting it may be a more effective treatment option for advanced CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution. Gottlieb, SL., Wolfe, JT., Fox, FE., et al.[2019]

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, a monoclonal antibody targeting CCR4, has been studied in 444 adult patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) and adult T-cell leukemia/lymphoma (ATL), showing its potential as an effective treatment option for these rare lymphomas.

The pharmacokinetic model developed from the data indicates that factors like albumin levels and hepatic function significantly influence the drug's clearance, which can help optimize dosing and improve treatment outcomes in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Modeling of Mogamulizumab in Adults With Cutaneous T-Cell Lymphoma or Adult T-Cell Lymphoma. Mukai, M., Maeda, H., Narushima, K., et al.[2021]

Extracorporeal photopheresis (ECP) has shown promising efficacy in treating early-stage cutaneous T-cell lymphoma (CTCL), with response rates ranging from 33% to 88% based on a review of 16 reports involving at least 124 patients.

ECP has a very low side effect profile compared to other treatments, suggesting it could be a beneficial option for patients with early-stage CTCL, although more randomized prospective studies are needed to confirm its effectiveness in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of extracorporeal photopheresis in early-stage (IA, IB, and IIA) cutaneous T-cell lymphoma. Miller, JD., Kirkland, EB., Domingo, DS., et al.[2007]

Photopheresis, an FDA-approved immunotherapy for cutaneous T-cell lymphoma (CTCL), showed that 25% of patients achieved complete remission, while half experienced clinical improvement, especially when treatment was initiated early in the erythrodermic stage.

Patients treated with photopheresis had an average survival of about 50 weeks, which is significantly longer than the 30 weeks reported for those receiving conventional therapies, indicating its potential effectiveness in managing CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The application of photopheresis in the therapy of cancerous and autoimmune diseases]. Dall'Amico, R., Zacchello, G., Heald, P.[2006]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38852942/

Chart review study of real-world clinical outcomes in ... This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients.

2. tandfonline.com tandfonline.com/doi/full/10.1080/09546634.2024.2360568

Chart review study of real-world clinical outcomes in ... In CTCL, ECP is associated with a 31-86% overall response rate (including complete and partial response), depending on subtype, stage, and concomitant therapies ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3078/500109/A-Retrospective-Study-of-Extracorporeal

A Retrospective Study of Extracorporeal Photopheresis (ECP ... Our results showed the contemporary ECP therapy had excellent efficacy in SS and AS-MF (ORR 77%). Many pts achieved durable remission (5-year PFS 58%).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123096805

A Retrospective Study of Extracorporeal Photopheresis ... Our results showed the contemporary ECP therapy had excellent efficacy in SS and AS-MF (ORR 77%). Many pts achieved durable remission (5-year PFS 58%).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3434329/

Clinical Results of Extracorporeal Photopheresis - PMC It has been used successfully for more than 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft- ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01140-2/fulltext

P5-2 Efficacy and safety of extracorporeal photopheresis ... When compared to other treatment strategies, all studies reviewed indicated that ECP was a consistent and safe therapy, with no grade 3 or 4 ECP-related adverse ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0190962296901188

Long-term follow-up of patients with cutaneous T-cell ... Median survival time for the entire cohort was 96 months (range, 16 to 152 months). An assessment of early response after 6 to 8 months of ECP had a sensitivity ...

8. prnewswire.com prnewswire.com/news-releases/new-data-on-patients-with-cutaneous-t-cell-lymphoma-treated-with-extracorporeal-photopheresis-from-a-retrospective-study-presented-at-the-american-society-of-hematology-annual-meeting-301442694.html

New Data on Patients with Cutaneous T-cell Lymphoma ... Clinical outcomes collected every three months during treatment for up to 18 months included the BSA affected, appearance of new skin lesions ...

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1669015/full

Extracorporeal photopheresis therapy rapidly changes the ... Extracorporeal photopheresis (ECP) is an established, effective and excellently tolerable CTCL therapy, that can also be applied for the treatment of graft vs.