Study of Mogamulizumab With DA-EPOCH or CHOEP in Patients With Aggressive T-cell Lymphoma

April 9, 2026 updated by: Tarsheen Sethi, Yale University

Phase II Study of Mogamulizumab With DA-EPOCH or CHOEP in Patients With Aggressive T-cell Lymphoma

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single arm, open label, multicenter phase II study of DA-EPOCH or CHOEP and Mogamulizumab in patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T-cell lymphomas including ATLL and transformed Mycosis Fungoides/Sézary syndrome (MF/SS). The investigators hypothesize that this combination is effective and will produce a CR rate that is statistically larger than 40%, a rate based on historical data from the current standard of care. DA-EPOCH or CHOEP and Mogamulizumab will be administered for 6 cycles and depending on the histology, consolidative strategies including SCT will be considered. Response assessments will occur at pre-specified intervals. Dose adjustments for specific toxicities with drugs are detailed in the protocol. Based on statistical analysis, a maximum of 22 patients will need to be accrued to obtain a sample of 19 evaluable patients for disease response.

Study Type

Interventional

Enrollment (Estimated)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center, Clinical Trials Office
        • Principal Investigator:
          • Tarsheen Sethi, MD
        • Contact:
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Roshan Asrani, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male/female patients who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (TNHL) will be enrolled in this study.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 unless compromised by lymphoma with anticipated benefit from chemotherapy as determined and documented by the investigator.

  3. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including but not limited to:

    • Peripheral T-cell lymphoma not otherwise specified (PTCL nos)
    • Angioimmunoblastic T-cell lymphoma (AITL)
    • Anaplastic large-cell lymphoma (ALCL)
    • Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome patients for whom multi-agent chemotherapy is indicated
    • Transformed mycosis fungoides/Sézary syndrome
    • Enteropathy-associated T-cell lymphoma (EATL)
    • Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
    • Hepatosplenic T- cell lymphomas
    • Gamma delta T-cell lymphomas
    • Adult T-cell lymphoma leukemia (ATLL)
    • T-prolymphocytic leukemia with nodal or visceral involvement
  4. Prior therapy- patients with aggressive T-cell lymphoma may have received one cycle of CHOP, CHOEP or EPOCH before enrollment, if necessary, to control the disease.
  5. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target lesion ≥ 1.5 cm

  6. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    • Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR
    • A woman of childbearing potential (WOCBP) - see Appendix 4 for definition of WOCBP - must have a negative serum or urine pregnancy test during screening and must agree to follow instructions for using acceptable contraception (Appendix 5) from the time of signing consent, and at least 180 days (6 months) after her final dose of mogamulizumab.
  7. A male patient must agree to use a contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least at least 180 days (6 months) after her final dose of mogamulizumab and refrain from donating sperm during this period.
  8. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of protocol-indicated treatment unless compromised by disease involvement of bone marrow, spleen, or liver as determined and documented by the investigator.
  9. Patients previously treated with anti-CD4 antibody or alemtuzumab are eligible provided their CD4+ cell counts are ≥ 200/mm.

Exclusion Criteria:

  1. Has received prior systemic anti-cancer therapy including investigational agents ≤ 3 weeks prior to first dose of study treatment on Cycle 1, Day 1. Skin directed treatments, including topicals and radiation within 2 weeks of study treatment. However, patients with rapidly progressive malignant disease may be enrolled prior to this period after discussion with the sponsor investigator.
  2. Has received radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  3. If patient received major surgery, participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  4. Patients on any immunomodulatory drug for concomitant or intercurrent conditions other than T-cell lymphoma or who have received any of these agents within 4 weeks of treatment, including but not limited to the following, will be excluded: low dose or oral methotrexate; azathioprine; iv immunoglobulin; low dose or oral cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; leflunomide; adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β IL-2 and natalizumab. . Concurrent use of topical steroids or therapies for CTCL is allowed as indicated in the protocol.
  5. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test within 72 hours of treatment start. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

  6. Has received a live vaccine within 30 days prior to the first dose of study drug.

    Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg,FluMist®) are live attenuated vaccines and are not allowed.

  7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

    Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

  8. Active uncontrolled infection requiring systemic therapy (patients must be afebrile for ≥ 48 hours and off antibiotics prior to treatment). If fever is attributed to tumor fever (B symptom) then these criteria would not apply.
  9. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure (Appendix 4).
  10. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided participants are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  11. Diagnosed with a malignancy, not treated under the study (hormonal therapy for breast or prostate cancer excepted), in the past 2 years. However, patients with nonmelanoma skin cancers, melanoma in situ, localized cancer of the prostate with current prostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast with in the past 2 years may enroll as long as there is no current evidence of disease.
  12. Known severe hypersensitivity (≥Grade 3) to mogamulizumab and/or any of its excipients and /or EPOCH/or CHOEP or any of its excipients.
  13. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
  14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  15. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  16. Has a known history of active TB (Bacillus Tuberculosis).
  17. Prior allogeneic stem cell transplant within last 2 years or active graft vs. host disease (GVHD).
  18. Known active autoimmune disease will be excluded if the disease requires active medical treatment. (For example, Graves' disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mogamulizumab + DA-EPOCH or CHOEP

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.
Drug: DA-EPOCH Protocol
EPOCH is an intensive chemotherapy regimen intended for treatment of aggressive non-Hodgkin's lymphoma.
Other Names:
  • dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone
Drug: Mogamulizumab

Mogamulizumab is a defucosylated, humanized, monoclonal antibody (Mab) with enhanced antibody dependent cellular cytotoxicity that binds to CCR4. The lack of fucose results in the antibody eliciting more potent ADCC than conventionally produced antibodies. Mogamulizumab is devoid of complement dependent cytotoxicity.

CC Chemokine receptor 4 is over expressed on the surfaces of cells comprising several T-cell malignancies such as peripheral T-cell lymphoma (PTCL) and CTCL and is a potential target for anti-neoplastic therapy in these disorders.

Other Names:
  • Poteligeo
Drug: CHOEP protocol
CHOEP is an intensive chemotherapy intended for treatment of aggressive t-cell lymphoma.
Other Names:
  • dose-adjusted Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Etoposide, Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH or CHOEP
Time Frame: 6 cycles (126 Days)
As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)
6 cycles (126 Days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: 2 years
Defined as the time from enrollment to earliest of progression, death or follow-up
2 years
Time to best response
Time Frame: 2 years
Defined as the time from treatment initiation to best response
2 years
Overall survival (OS)
Time Frame: 2 years
defined as time from the time from enrollment to earlier of death or last follow-up
2 years
Duration of response
Time Frame: 2 Years
(including both scenarios -censored at the time of subsequent therapy without disease progression, such as stem cell transplant and total duration including after SCT)
2 Years
Occurrence of toxicity
Time Frame: 2 years
using the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading.
2 years
Overall response rate
Time Frame: 2 years
Defined as the percentage of patients whose cancer shows a partial response or complete response
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

Kyowa Kirin, Inc.

Investigators

  • Principal Investigator: Tarsheen Sethi, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2024

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

July 24, 2023

First Submitted That Met QC Criteria

August 14, 2023

First Posted (Actual)

August 18, 2023

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000037447
  • 000 (Other Identifier: YCTG)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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