Photopheresis + Mogamulizumab for Cutaneous T-Cell Lymphoma

Recruiting at 1 trial location

Overseen by Christiane Querfeld, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Prior mogamulizumab, Active infection, Autoimmune disorders, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of extracorporeal photopheresis (ECP) and mogamulizumab in treating patients with erythrodermic cutaneous T cell lymphoma (CTCL), a type of skin lymphoma. CTCL is a rare type of cancer that begins in the white blood cells called T cells. Erythrodermic is a widespread red rash that may cover most of the body. ECP is a medical treatment that removes blood with a machine, isolates white blood cells and exposes them to ultra violet light, then returns the cells to the body. Mogamulizumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving mogamulizumab with ECP may work together to kill the tumor cells directly (with mogamulizumab) and boost immune response to cancer (with ECP).

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.

What data supports the effectiveness of the treatment Photopheresis + Mogamulizumab for Cutaneous T-Cell Lymphoma?

Photopheresis has shown promise in treating cutaneous T-cell lymphoma, with some patients experiencing complete remission or clinical improvement. Mogamulizumab has been effective in controlling the disease and improving quality of life for patients with cutaneous T-cell lymphomas, including mycosis fungoides and Sèzary syndrome. ^{1 2 3 4 5}

What is known about the safety of Mogamulizumab for Cutaneous T-Cell Lymphoma?

Mogamulizumab has been studied in clinical trials for cutaneous T-cell lymphoma, showing common side effects like rash, fatigue, and diarrhea. Serious reactions can include infections and infusion-related issues, but overall, it has a manageable safety profile. ^{2 6 7 8 9}

How is the treatment of Photopheresis + Mogamulizumab unique for cutaneous T-cell lymphoma?

This treatment combines photopheresis, which uses light to stimulate the immune system against cancer cells, with mogamulizumab, a drug that targets specific receptors on malignant T-cells to enhance the body's immune response. This combination offers a novel approach by potentially improving outcomes for patients who do not respond well to other treatments. ^{1 2 3 10 11}

Research Team

Christiane Querfeld, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

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

Exclusion Criteria

I do not have any other active cancer.

I require dialysis for kidney failure.

I have had a stem cell transplant before.

Trial Timeline

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

Treatment Details

Interventions

• Extracorporeal Photopheresis (Procedure)
• Mogamulizumab (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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-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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

[The application of photopheresis in the therapy of cancerous and autoimmune diseases]. [2006]

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

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

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

Therapeutic applications of photopheresis. [2007]

4. United States 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. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis. [2023]

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]

8. United States 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Modeling of Mogamulizumab in Adults With Cutaneous T-Cell Lymphoma or Adult T-Cell Lymphoma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Review of extracorporeal photopheresis in early-stage (IA, IB, and IIA) cutaneous T-cell lymphoma. [2007]

11. England 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. [2018]