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

NCT05996185 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2000037447000
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

T Cell Lymphoma; T-cell Lymphoma

Keywords

Relapsed; Refractory; Adult T-Cell Leukemia/Lymphoma; Cutaneous T-cell lymphoma; Mycosis Fungoides/Sézary syndrome; DA-EPOCH; Mogamulizumab; CHOEP

Outcome Measures

Primary Outcomes (1)

• Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH or CHOEP

  As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)

  6 cycles (126 Days)

Secondary Outcomes (6)

• Occurrence of toxicity

  2 years

• Progression free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

• Duration of response

  2 Years

• Time to best response

  2 years

Study Arms (1)

Mogamulizumab + DA-EPOCH or CHOEP

EXPERIMENTAL

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: Mogamulizumab; Drug: DA-EPOCH Protocol; Drug: CHOEP protocol

Interventions

Mogamulizumab DRUG

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.

Also known as: Poteligeo

Mogamulizumab + DA-EPOCH or CHOEP

DA-EPOCH Protocol DRUG

EPOCH is an intensive chemotherapy regimen intended for treatment of aggressive non-Hodgkin's lymphoma.

Also known as: dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone

Mogamulizumab + DA-EPOCH or CHOEP

CHOEP protocol DRUG

CHOEP is an intensive chemotherapy intended for treatment of aggressive t-cell lymphoma.

Also known as: dose-adjusted Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Etoposide, Prednisone

Mogamulizumab + DA-EPOCH or CHOEP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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
• 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.

You may not qualify if:

• 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.
• 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.
• If patient received major surgery, participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• 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.
• 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.
• 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.
• 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.
• 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.
• Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure (Appendix 4).
• 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.
• 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.
• Known severe hypersensitivity (≥Grade 3) to mogamulizumab and/or any of its excipients and /or EPOCH/or CHOEP or any of its excipients.
• Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.

Sponsors & Collaborators

• Yale University: lead
• Kyowa Kirin, Inc.: collaborator

Study Sites (2)

Yale Cancer Center, Clinical Trials Office

New Haven, Connecticut, 06510, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

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MeSH Terms

Conditions

Lymphoma, T-Cell; Recurrence; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell, Cutaneous

Interventions

mogamulizumab; EPOCH protocol; Doxorubicin; Cyclophosphamide; Vincristine; Prednisone; CHOEP protocol; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Tarsheen Sethi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carole Ramm

CONTACT

(203) 785-4095; carole.ramm@yale.edu

Stephanie Ladd

CONTACT

954-895-0576; stephanie.ladd@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Selection of regimen will be at the treating investigator's discretion.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSCI, Assistant Professor of Medicine

Model Details: 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

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 18, 2023
• Study Start: October 9, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-02

Locations

US (2)