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

Trial Summary

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.

What data supports the effectiveness of the drug mogamulizumab for preventing adult T-cell leukemia/lymphoma?

Research shows that mogamulizumab, when used in combination with chemotherapy, improved the four-year survival rate for patients with aggressive adult T-cell leukemia/lymphoma compared to chemotherapy alone. This suggests that mogamulizumab can be an effective treatment option, especially for those who cannot undergo a transplant. ^{1 2 3 4 5}

Is mogamulizumab safe for humans?

Mogamulizumab has been studied in patients with adult T-cell leukemia/lymphoma, and while it shows potential benefits, it can cause side effects. Common side effects include infusion-related reactions and low platelet counts, and serious side effects have been reported in some cases, so patients need careful monitoring. ^{3 4 6 7 8}

How is the drug mogamulizumab unique in treating adult T-cell leukemia/lymphoma?

Mogamulizumab is unique because it is a humanized antibody that targets the CCR4 receptor on cancer cells, enhancing the body's immune response to attack these cells. It is effective at lower doses compared to other treatments and has shown promising results in patients with relapsed or refractory adult T-cell leukemia/lymphoma, offering a new option where conventional treatments often fail. ^{3 4 7 9 10}

What is the purpose of this trial?

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 (ATL) in people who are at higher risk for this type of cancer because they are infected with the HTLV-1 virus and because of changes seen in some of their immune system cells called T-cells.

Research Team

Steven M. Horwitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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): Hemoglobin: ≥9.0 g/dL

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

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.

Patients with uncontrolled psychiatric disorder, epilepsy, or dementia

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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-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]

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 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]

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, 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]

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]

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]

References

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

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma. [2018]

2. 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]

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of mogamulizumab for relapsed/refractory aggressive adult T-cell leukemia/lymphoma: A retrospective analysis. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Beneficial impact of first-line mogamulizumab-containing chemotherapy in adult T-cell leukaemia-lymphoma. [2022]

6. Japan 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. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma. [2018]

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

Mogamulizumab: An Anti-CC Chemokine Receptor 4 Antibody for T-Cell Lymphomas. [2020]