Mogamulizumab + DA-EPOCH for T-Cell Lymphoma

Recruiting at 2 trial locations

Overseen By Carole Ramm

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sethi

Must not be taking: Immunomodulatory drugs

Disqualifiers: Pregnancy, Active infection, CNS metastases, 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: 6

Duration: 18 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for people with aggressive T-cell lymphoma, including those newly diagnosed or with a type that has returned or not responded to previous treatments. The study combines mogamulizumab, a targeted therapy, with a standard chemotherapy regimen called DA-EPOCH. The goal is to determine if this combination more effectively treats the cancer. It suits patients with T-cell non-Hodgkin lymphoma who may have previously tried treatments like CHOP or EPOCH. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on certain immunomodulatory drugs or have received them within 4 weeks of treatment, you may be excluded from participating. It's best to discuss your specific medications with the trial team.

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

Research shows that adding mogamulizumab to the usual chemotherapy treatment, DA-EPOCH, appears safe. Mogamulizumab has been used in other treatments for over five years and has consistently proven safe. No increases in side effects have occurred when the drug is administered intravenously, suggesting it might be well-tolerated with DA-EPOCH. Notably, mogamulizumab is already approved for some blood cancers, which supports its safety.

For those considering joining the trial, this means that while the treatment is still under study, past evidence suggests it is generally safe. As always, discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Mogamulizumab combined with the DA-EPOCH protocol for T-cell lymphoma because it offers a novel approach compared to traditional treatments like CHOP or EPOCH alone. Unlike standard therapies, Mogamulizumab is a monoclonal antibody that specifically targets CCR4, a protein found on the surface of certain T-cell lymphomas, potentially leading to more precise attacks on cancer cells. Additionally, the combination of Mogamulizumab with DA-EPOCH may enhance the effectiveness of chemotherapy, providing a synergistic effect that could improve outcomes for patients. This innovative strategy could offer a more targeted and potentially more effective treatment option for those battling this challenging type of lymphoma.

What evidence suggests that this trial's treatments could be effective for T-cell lymphoma?

Research has shown that mogamulizumab can help treat certain skin lymphomas, such as mycosis fungoides and Sézary syndrome, especially when other treatments have failed. DA-EPOCH is a potent chemotherapy used for aggressive lymphomas. This trial tests the combination of mogamulizumab and DA-EPOCH, mixing a targeted treatment with powerful chemotherapy. Early results suggest that using them together might improve outcomes for aggressive T-cell lymphomas, including Adult T-cell leukemia/lymphoma (ATLL). Although more research is needed, this combination appears promising for treating difficult lymphomas. ^{1 5 6 7 8}

Who Is on the Research Team?

Tarsheen Sethi, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Adults with confirmed aggressive T-cell Non-Hodgkin lymphoma, including various subtypes like PTCL and CTCL, can join this trial. They should have a decent performance status (able to carry out daily activities) and may have had one cycle of certain chemotherapies. Women must not be pregnant or breastfeeding and agree to use contraception; men also need to commit to using contraception.

Inclusion Criteria

I have received specific chemotherapy for aggressive T cell lymphoma.

I am not pregnant or breastfeeding.

My organs and bone marrow are working well.

Exclusion Criteria

I have not had cancer treatment recently.

I have recently undergone radiotherapy.

I am taking drugs that modify my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Mogamulizumab and DA-EPOCH for 6 cycles, with Mogamulizumab administered on days 1, 8, 15 of the first cycle and day 1 of subsequent cycles, and DA-EPOCH on day 1 of each cycle

18 weeks

6 cycles (in-person visits for each cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for complete response and occurrence of toxicity

2 years

Extension/Long-term follow-up

Participants are monitored for progression-free survival, overall survival, and duration of response

2 years

What Are the Treatments Tested in This Trial?

Interventions

• DA-EPOCH Protocol
• Mogamulizumab

Trial Overview

The study is testing the effectiveness of Mogamulizumab when added to the DA-EPOCH chemotherapy regimen in patients with newly diagnosed or relapsed/refractory aggressive T cell lymphoma. It's a Phase II trial where all participants receive this combination treatment.

How Is the Trial Designed?

Group I: Mogamulizumab + DA-EPOCH or CHOEP Experimental Treatment 3 Interventions

All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1. Cycles 2 to 6: Mogamulizumab on day 1 with DA-EPOCH or CHOEP Mogamulizumab will be administered modified to a 21-day cycle in combination with chemotherapy. Subjects will receive 1.0 mg/kg of mogamulizumab as an IV infusion over at least 1 hour on Days 1, 8, 15 of the first cycle and Day 1 for the subsequent cycles. This is based on prior studies with mogamulizumab in combination of chemotherapy.(15) This dosing regimen will ensure the first 4 doses are given weekly at a dose of 1 mg/kg. Subsequent dosing on a 21-day schedule to coincide with the frequency of administration of DA-EPOCH or CHOEP to allow for simpler co-administration of the study drugs. In addition, this study proposes to leverage the immunomodulatory role of mogamulizumab, the dosing for this has not been previously established or explored.

DA-EPOCH Protocol is already approved in United States, European Union for the following indications:

Approved in United States as DA-EPOCH for:

• Diffuse Large B-Cell Lymphoma (DLBCL)
• Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
• Burkitt Lymphoma
• Aggressive Non-Hodgkin Lymphoma (NHL)

Approved in European Union as DA-EPOCH for:

• Diffuse Large B-Cell Lymphoma (DLBCL)
• Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
• Burkitt Lymphoma
• Aggressive Non-Hodgkin Lymphoma (NHL)

Who Is Running the Clinical Trial?

Sethi

Lead Sponsor

Trials

2

Recruited

70+

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Tarsheen Sethi

Lead Sponsor

Trials

2

Recruited

70+

Kyowa Kirin, Inc.

Industry Sponsor

Trials

49

Recruited

5,700+

Published Research Related to This Trial

In a phase III study involving 491 patients with diffuse large B-cell lymphoma, the more intensive treatment regimen DA-EPOCH-R did not show a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) compared to the standard R-CHOP regimen, with 2-year PFS rates of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP.

DA-EPOCH-R was associated with a higher incidence of severe adverse events, including infections and febrile neutropenia, indicating that while it is a more intensive treatment, it does not provide additional survival benefits and carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Bartlett, NL., Wilson, WH., Jung, SH., et al.[2021]

The DA-EPOCH-R treatment regimen shows a 74% response rate and a 59% complete response rate in older patients (median age 69) with high-risk diffuse large B-cell lymphoma, indicating its efficacy in this population.

While the three-year progression-free survival (53%) and overall survival (58%) rates are promising, there is a notable treatment-related mortality rate of 13%, suggesting that patients with poorer performance status may need less intensive therapies to avoid excessive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Mitrovic, Z., Dujmovic, D., Jaksic, O., et al.[2023]

In a study of 73 patients with aggressive B-cell non-Hodgkin lymphoma treated with the da-EPOCH-R regimen, the use of pegylated GCSF (peg-GCSF) was found to be as effective as daily GCSF in achieving the desired chemotherapy dose levels.

The rates of unplanned hospitalizations and overall survival were similar between patients receiving peg-GCSF and those receiving daily GCSF, suggesting that peg-GCSF is a safe and effective alternative for supporting chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated GCSF Can Be Used With First-Line da-EPOCH-R Without Compromising Dose Intensity, Safety, or Efficacy. Reddy, P., Kanan, S., Cowan, A., et al.[2019]

In a study of 33 patients with poor prognosis diffuse large B-cell lymphoma (DLBCL), the DA-EPOCH-R treatment regimen resulted in an impressive 83.8% complete remission rate, demonstrating its efficacy in this challenging patient population.

The treatment was associated with manageable safety concerns, with significant neutropenia occurring in 52% of cycles, but overall, the regimen showed a favorable toxicity profile and could be administered as an outpatient, potentially improving patient compliance and reducing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. García-Suárez, J., Bañas, H., Arribas, I., et al.[2015]

In a study of 136 patients with aggressive non-Hodgkin lymphoma treated with dose-adjusted EPOCH chemotherapy, the overall response rate was 82%, indicating that this treatment is effective for both B- and T-cell types of the disease.

Factors such as current smoking, presence of disease in the bone marrow, and the number of treatment cycles completed were identified as independent predictors of death and relapse, highlighting the importance of these factors in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma. Lamar, ZS., Fino, N., Palmer, J., et al.[2018]

In a multicenter phase II study involving 41 patients with untreated peripheral T-cell lymphoma, the dose-adjusted EPOCH therapy achieved a high overall response rate of 78% and a complete response rate of 61%, indicating its efficacy as a first-line treatment.

The treatment demonstrated a tolerable safety profile, with the most common severe side effects being neutropenia (74.5%) and anemia (40.8%), suggesting that while effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Maeda, Y., Nishimori, H., Yoshida, I., et al.[2022]

In a study of 43 patients treated with DA-EPOCH-R for aggressive non-Hodgkin lymphoma, 39.5% experienced line-associated complications (LACs), which were significantly higher compared to 18.2% in a concurrent R-CHOP cohort.

Among the LACs in the DA-EPOCH-R group, 41% were classified as grade 3 toxicity, with higher risks associated with a body mass index of 35 kg/m2 or more and the use of a peripherally inserted central catheter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications Associated With Dose-adjusted EPOCH-rituximab Therapy for Non-Hodgkin Lymphoma. David, RJ., Baran, A., Loh, KP., et al.[2019]

Outpatient administration of the DA-EPOCH chemotherapy regimen for aggressive B-cell lymphomas was found to be safe, with zero hospitalizations required during treatment and a total of 965 hospital days saved.

The transition of DA-EPOCH to an outpatient setting not only proved feasible but also resulted in significant cost savings, with an annual positive financial impact of $1,444,548 for the cancer center.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and financial analysis of outpatient dose-adjusted EPOCH for B-cell lymphoma at a tertiary comprehensive cancer center. Li, W., Richter, KA., Tobon, KA., et al.[2021]

In a study of 4 patients with diffuse large B cell lymphoma in the gastrointestinal tract, the R-DA-EPOCH treatment regimen resulted in complete remission for 3 patients, indicating good short-term efficacy.

However, one patient died from a severe infection, highlighting the need for careful monitoring of safety during treatment, and the long-term effectiveness of R-DA-EPOCH requires further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rituximab combined with EPOCH regimen for treatment of diffuse large B cell lymphoma of the gastrointestinal tract: analysis of 4 cases]. Hu, RH., Sun, WL., Zhao, H., et al.[2018]

In a study of 149 patients with aggressive lymphoma, the dose-adjusted EPOCH regimen (with or without rituximab) showed a high complete response rate of 79%, indicating strong efficacy in treating this type of cancer.

The treatment was well-tolerated with no treatment-related deaths, although 55% of patients experienced febrile neutropenia, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data. Matsuda, S., Suzuki, R., Takahashi, T., et al.[2022]

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