Mogamulizumab for Preventing Adult T-Cell Leukemia/Lymphoma

Recruiting at 6 trial locations

Overseen By Alison Moskowitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Interferon alpha

Disqualifiers: Hepatitis, Tuberculosis, Heart failure, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mogamulizumab (also known as Poteligeo) to determine its effectiveness in preventing adult T-cell leukemia/lymphoma in individuals at higher risk due to an HTLV-1 virus infection. The study includes two groups: one receives the drug every 6 weeks, and the other every 12 weeks. Suitable candidates for this trial have a positive HTLV-1 virus test and specific immune cell changes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken immunosuppressants, interferon alpha products, or certain supplements recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that mogamulizumab is likely to be safe for humans?

Research has shown that mogamulizumab, also known as POTELIGEO, is generally safe. Long-term studies indicate that most people tolerate it well. Some patients in trials experienced side effects, but these were usually manageable. This treatment has proven effective and safe for conditions like cutaneous T-cell lymphoma, a type of skin cancer. While all treatments carry some risks, current data suggests that mogamulizumab's side effects are often mild to moderate. This indicates it may be safe for preventing adult T-cell leukemia/lymphoma in high-risk patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mogamulizumab is unique because it targets the CCR4 protein on cancerous T-cells, a different mechanism than most standard treatments for adult T-cell leukemia/lymphoma, which typically involve chemotherapy and stem cell transplants. Researchers are excited about mogamulizumab as it offers a more targeted approach, potentially reducing the damage to healthy cells and minimizing side effects. Additionally, its administration schedule in the trial — either every 6 or 12 weeks — could offer more flexibility and convenience compared to traditional therapies.

What evidence suggests that mogamulizumab might be an effective treatment for preventing adult T-cell leukemia/lymphoma?

Research has shown that mogamulizumab may effectively treat adult T-cell leukemia/lymphoma (ATL). Studies have found that 65% of patients responded positively to the treatment. On average, patients lived about 7.4 months without disease progression, and their overall survival was around 16 months. Mogamulizumab, a monoclonal antibody, helps the immune system identify and attack cancer cells. In this trial, participants will receive mogamulizumab in one of two dosing schedules: every 6 weeks for 4 doses or every 12 weeks for 2 doses. This treatment is already approved for cutaneous T-cell lymphoma, suggesting it could also help prevent ATL in people at high risk. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven M. Horwitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people at high risk of developing adult T-cell leukemia/lymphoma (ATL) due to HTLV-1 infection and specific changes in their T-cells. The detailed eligibility criteria are not provided, but typically include health status and other factors relevant to the study.

Inclusion Criteria

Treatment Cohorts (Cohorts 1 and 2): Serum creatinine (Cr): ≤1.5x ULN

Treatment Cohorts (Cohorts 1 and 2): Hemoglobin: ≥9.0 g/dL

Treatment Cohorts (Cohorts 1 and 2): Blood oxygen saturation (SpO2): ≥90%

Exclusion Criteria

I haven't taken immunosuppressants or interferon alpha in the last 6 months.

I don't have conditions that could worsen with KW-0761, as per my doctor.

Women who are pregnant, breastfeeding, who may be pregnant, or wish to bear children while receiving treatment or within 3 months of last dose of mogamulizumab

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mogamulizumab to prevent the development of adult T-cell leukemia/lymphoma

12 weeks

4 visits (in-person) for Cohort 2, 2 visits (in-person) for Cohort 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Mogamulizumab

Trial Overview The trial is testing mogamulizumab's effectiveness in preventing ATL in individuals with HTLV-1. It aims to see if this drug can stop the cancer from developing by targeting changes in immune system cells.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

Cohort 2: 0.3 mg/kg of mogamulizumab every 6 weeks, for 4 total doses

Group II: Cohort 1 Experimental Treatment 1 Intervention

Cohort 1: 0.3 mg/kg of mogamulizumab every 12 weeks, for 2 total doses

Mogamulizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in United States as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Canada as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Japan as Poteligeo for:

• Adult T-cell leukemia-lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Mogamulizumab is an FDA-approved monoclonal antibody that targets the CCR4 receptor, showing significant improvement in progression-free survival for patients with relapsed or refractory mycosis fungoides or Sézary syndrome compared to vorinostat.

While mogamulizumab offers a new treatment option for T-cell lymphomas, it is associated with serious adverse events such as infusion reactions and increased risk of graft-versus-host disease in certain settings, highlighting the need for careful patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab: An Anti-CC Chemokine Receptor 4 Antibody for T-Cell Lymphomas. Moore, DC., Elmes, JB., Shibu, PA., 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]

In a study of 39 transplant-ineligible patients with untreated aggressive adult T-cell leukaemia-lymphoma (ATL), those receiving chemotherapy combined with mogamulizumab (Mog) had a significantly higher four-year overall survival rate of 46.3% compared to 20.6% for those receiving chemotherapy alone.

The survival benefit of Mog was evident even among elderly patients, suggesting that Mog-containing treatment could be an effective first-line strategy for this population with ATL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial impact of first-line mogamulizumab-containing chemotherapy in adult T-cell leukaemia-lymphoma. Shichijo, T., Nosaka, K., Tatetsu, H., et al.[2022]

Mogamulizumab significantly improves overall survival in patients with adult T-cell leukemia/lymphoma (ATL), as shown in a study of 125 patients treated in Hokkaido, Japan, from 2010 to 2014.

While mogamulizumab enhances survival rates, its use in patients undergoing hematopoietic stem cell transplantation (HSCT) may increase the risk of severe acute graft-versus-host disease (aGVHD), highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma. Iyama, S., Sato, T., Ohnishi, H., et al.[2018]

In a study of 42 patients with relapsed/refractory adult T-cell leukemia/lymphoma (ATL), mogamulizumab demonstrated an overall response rate of 54.2%, indicating its efficacy in a real-world clinical setting.

Patients with acute-type ATL treated with mogamulizumab had a median survival time of 15.1 months and a 1-year overall survival rate of 63.6%, suggesting that the drug significantly improves outcomes, particularly in those with skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of mogamulizumab for relapsed/refractory aggressive adult T-cell leukemia/lymphoma: A retrospective analysis. Satake, A., Konishi, A., Azuma, Y., et al.[2021]

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]

In a study of 484 patients with relapsed or refractory adult T-cell leukemia-lymphoma treated with mogamulizumab, the overall response rate was 57.7%, indicating that the treatment is effective for this patient population.

While mogamulizumab shows acceptable tolerability, 74% of patients experienced adverse drug reactions, with 35.7% classified as serious and 6.2% fatal, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance. Ishitsuka, K., Yurimoto, S., Kawamura, K., et al.[2022]

In a phase II study involving 71 patients with relapsed/refractory adult T-cell leukemia/lymphoma (ATL), mogamulizumab demonstrated a confirmed overall response rate (cORR) of 11%, significantly outperforming the chemotherapy arm, which showed no tumor response.

Mogamulizumab was associated with a tolerable safety profile, with the most common severe side effects being infusion-related reactions and thrombocytopenia, each occurring in 9% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma. Phillips, AA., Fields, PA., Hermine, O., et al.[2022]

Mogamulizumab, an anti-CCR4 receptor antibody, shows promising antitumor activity in treating aggressive T-cell neoplasms like adult T-cell leukemia/lymphoma (ATL) at lower doses compared to other monoclonal antibodies.

Clinical trials indicate that mogamulizumab is effective and well tolerated in patients with relapsed/refractory ATL, leading to its recent regulatory approval in Japan and ongoing evaluations in the U.S. and Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma. de Lartigue, J.[2017]

Mogamulizumab, a monoclonal antibody targeting CCR4 on malignant T-cells, has shown overall response rates of 31-50% in treating adult T-cell leukemia-lymphoma (ATL), indicating its significant efficacy as a treatment option.

The treatment is associated with common adverse events such as lymphocytopenia and infusion reactions, but it has been approved in Japan and may be used as a bridge therapy before stem cell transplantation or in combination with other chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma. Winsett, FT., Lewis, DJ., Duvic, M.[2018]

Citations

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Mogamulizumab for adult T-cell leukemia-lymphoma The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33091125/

Mogamulizumab for adult T-cell leukemia-lymphoma The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A ...

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Efficacy and manageable toxicity of mogamulizumab in a ... Mogamulizumab, a CCR4-targeting monoclonal antibody, is FDA-approved for relapsed cutaneous T-cell lymphoma and has shown efficacy in Japanese ...

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A Study of Mogamulizumab to Prevent Adult T-cell ... The purpose of this study is to find out whether the study drug mogamulizumab is effective in preventing the development of adult T-cell leukemia/lymphoma ...

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Safety & Adverse Reactions | POTELIGEO® (mogamulizumab ... POTELIGEO has a consistent safety profile with up to 5 years of data · Long-term exposure was defined as >351 days of exposure to POTELIGEO. · Adverse reactions ...

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Kyowa Kirin Announces Final Safety Data of POTELIGEO® ... MAVORIC is the first pivotal trial in cutaneous T-cell lymphoma (CTCL) to use progression free survival (PFS) as a primary endpoint.

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Safety and efficacy profile of mogamulizumab (Poteligeo) in ... Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in ...

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Mogamulizumab-kpkc (Poteligeo) - Medical Clinical Policy ... Aetna considers mogamulizumab-kpkc (Poteligeo) intravenous infusion medically necessary for the treatment of any of the following conditions: Adult T-cell ...

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761051Orig1s000 - accessdata.fda.gov POTELIGEO (mogamulizumab-kpkc). 22. Mogamulizumab also mediated the lysis of adult T cell leukemia-lymphoma (ATL) patient- derived tumor cells ...