Mogamulizumab + DA-EPOCH for T-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Stephanie Ladd

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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Single- arm Phase II study evaluating the combination of mogamulizumab (MOGA) added on top of standard of care dose adjusted EPOCH (DA-EPOCH) in patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T cell lymphoma including patients with Adult T-cell leukemia/lymphoma (ATLL).

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.

What data supports the effectiveness of the treatment Mogamulizumab + DA-EPOCH for T-Cell Lymphoma?

The DA-EPOCH treatment, which is part of the Mogamulizumab + DA-EPOCH therapy, has shown a high response rate and tolerable side effects in patients with peripheral T-cell lymphoma, with 78% of patients responding to the treatment and 61% achieving complete remission. ^{1 2 3 4 5}

Is the combination of Mogamulizumab and DA-EPOCH safe for humans?

The DA-EPOCH regimen, used for aggressive lymphomas, has been studied and found to be generally safe, with common side effects including neutropenia (low white blood cell count) and infections. There were no treatment-related deaths reported in the studies, but some patients experienced severe infections. Mogamulizumab, another component of the treatment, has been used in other conditions, but specific safety data for its combination with DA-EPOCH in T-cell lymphoma is not provided in the available studies. ^{1 2 5 6 7}

How is the treatment Mogamulizumab + DA-EPOCH for T-Cell Lymphoma different from other treatments?

Mogamulizumab + DA-EPOCH is unique because it combines a targeted therapy (mogamulizumab) with a dose-adjusted chemotherapy regimen (DA-EPOCH) to potentially improve outcomes for T-cell lymphoma, a condition with limited standard treatment options. This approach aims to enhance the effectiveness of chemotherapy by adjusting doses based on patient tolerance and adding a drug that specifically targets cancer cells. ^{1 4 8 9 10}

Research Team

Tarsheen Sethi

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Mogamulizumab + DA-EPOCH Experimental Treatment 2 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. Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH 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 dosing regimen will ensure the first 4 doses are given weekly at a dose of 1 mg/kg. Subsequent dosing will occur on a 21-day schedule to coincide with the frequency of administration of DA-EPOCH to allow for simpler co-administration of the study drugs.

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+

Findings from Research

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 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 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 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 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]

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 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 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]

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]

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]

References

1. England 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). [2023]

2. China 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]. [2018]

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

Pegylated GCSF Can Be Used With First-Line da-EPOCH-R Without Compromising Dose Intensity, Safety, or Efficacy. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and financial analysis of outpatient dose-adjusted EPOCH for B-cell lymphoma at a tertiary comprehensive cancer center. [2021]

7. England 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. [2015]

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

Complications Associated With Dose-adjusted EPOCH-rituximab Therapy for Non-Hodgkin Lymphoma. [2019]

9. United States 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. [2021]

10. United States 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. [2018]