Mogamulizumab + Low-Dose Total Skin Electron Beam Tx in Mycosis Fungoides & Sézary Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of the combination of LD-TSEBT and mogamulizumab in patients with MF and SS. And to evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS.

Detailed Description
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Primary Objective:To determine the efficacy of the combination of LD TSEBT and mogamulizumab in patients with MF and SS Secondary Objective: To evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS

Official Title
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A Phase 2 Single Center, Single Arm, Open Label Mogamulizumab Combined Upfront With Low Dose Total Skin Electron Beam Therapy (LD TSEBT) in Patients With Mycosis Fungoides (MF) and Sézary Syndrome (SS)

Conditions
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Sezary Syndrome, Mycosis Fungoides

Intervention / Treatment
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* Drug: Mogamulizumab
* Radiation: LD TSEBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stages 1B IV MF or SS 1 prior standard of care therapy Prior LD-TSEBT (> 3 months prior) and prior mogamulizumab is allowed, as long as progressive disease (PD) did not occur while on therapy, and did not discontinue due to toxicities ≥ 18 years of age The Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 All clinically-significant toxic effects of prior cancer therapy resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE, v 5.0). MF and a known history of non-complicated staphylococcus colonization/infection is eligible provided that stable doses of prophylactic antibiotics continue. The following minimum wash-out from previous treatments are required, if applicable. ≥ 4 weeks for retinoids, interferons, Vorinostat, romidepsin, pralatrexate, or other systemic anti-cancer/CTCL therapies ≥ 2 weeks for phototherapy, local radiation therapy ≥ 2 weeks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod) ≥ 12 weeks for total skin electron beam therapy ≥ 4 weeks for monoclonal antibodies; except > 12 weeks for alemtuzumab Rapidly progressive malignant disease may be enrolled prior to above periods after discussion with the Protocol Director. Adequate hematologic function Absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); or if known bone marrow involvement, then ANC ≥ 1,000 cells/μL (≥ 1,000/mm3) Platelets ≥ 100,000 cells/μL (≥ 100,000/mm3); or if known bone marrow involvement, then platelets ≥ 75,000 cells/μL (≥ 75,000/mm3). Adequate hepatic function Bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN). Exception: If Gilbert's syndrome; then ≤ 5 times ULN. Aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN; or ≤ 5.0 x ULN in the presence of known hepatic involvement by CTCL. Adequate renal function Serum creatinine ≤ 1.5 x ULN; or Calculated creatinine clearance > 50 mL/min using the Cockcroft Gault formula. If prior allogeneic hematopoietic stem cell transplant (HSCT), then must be free of graft vs host disease (GvHD) and receiving immunosuppressive therapy. Women of childbearing potential (WOCBP) must have a negative pregnancy test. WOCBP must agree to use effective contraception during the study and for 3 months after the last dose. Male participants and their female partners of child bearing potential must be willing to use an appropriate method of contraception during the study and for 3 months after the last dose. Exclusion Criteria: MF with limited disease (Stage IA) or central nervous system (CNS) disease Concomitant corticosteroid use. (with the exception that topical steroid and oral prednisone are allowed at ≤ 20 mg/day, if patient has been on a stable dose for at least 4 weeks prior to study treatment) Pregnant or breastfeeding Active autoimmune disease or history deemed by the investigator to be clinically significant Known human immunodeficiency virus (HIV) positivity; known human T-cell lymphotropic virus (HTLV-1) infection; or active hepatitis B or C. Active herpes simplex or herpes zoster. Those receiving prophylaxis for herpes and who started taking medication at least 30 days prior to the Screening Visit, and have no active signs of active infection, and whose last active infection was more than 6 months ago, may enter the study, and should continue to take the prescribed medication for the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LD TSEBT<br>Mogamulizumab with low dose total skin electron beam therapy. • LD (12 Gy) TSEBT will be initiated on Cycle 1 Day 2 (± 2 days) of mogamulizumab over 2 to 3 week period per standard of care (SOC), as tolerated. Mogamulizumab (1 mg/kg) will be administered over 60 minutes as follows (per SOC and FDA approved use in MF and SS): Cycle 1 only: Days1; 8; 15; and 22 (± 2 days) Cycle 2 and beyond: Day 1 and Day 15 (± 3 days) | Drug: Mogamulizumab<br>* Administered 1 mg/kg as an intravenous infusion over at least 60 minutes on Days 1, 8, 15, and 22 of the first 28 day cycle and on Days 1 and 15 of each subsequent cycle.<br>Radiation: LD TSEBT<br>* Patients will receive total skin dose of 12 Gy fractionated at 4 to 6 Gy per week, for 2-3 weeks<br>* Other names: Low-Dose (LD) Total skin electron beam therapy (TSEBT);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Response to treatment will be assessed as the number and proportion of participants who achieve either a complete response (CR) or partial response (PR). The outcome is reported as numbers without dispersion. Clinical response will be assessed as follows. CR: Complete disappearance of all clinical evidence of disease PR: Decrease in size or amount of measurable disease lesions Progressive disease (PD): Worsening of lesions; appearance of new lesions; or recurrence of lesions Stable disease (SD): Disease status that is neither CR, PR, nor PD. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-Next Significant Treatment (TTNT) | Time-to-next significant treatment (TTNT) will be assessed as the amount of time from starting study treatment through the initiation of any non study systemic therapy. The outcome will be reported as the median TTNT. | 3 years | 
| Progression free survival (PFS) | Progression free survival (PFS) will be assessed as the amount of time from starting study treatment to progression of disease (PD) or death due to any cause. | 12 months | 
| Duration of response (DOR) | Duration of response (DOR) will be assessed in those participants who achieve either a complete response (CR) or partial response (PR), and with duration as time to progressive disease or the initiation of a non-study systemic therapy. CR: Complete disappearance of all clinical evidence of disease PR: Decrease in size or amount of measurable disease lesions Progressive disease (PD): Worsening of lesions; appearance of new lesions; or recurrence of lesions Stable disease (SD): Disease status that is neither CR, PR, nor PD. | 12 months | 
| Patient reported Quality of Life (QoL) | The Skindex 29 survey was used to evaluate the effect of skin conditions on participant's quality of life (QoL). Surveys were administered at the beginning of every treatment cycle and continuing through up to 3 years of treatment. The survey is a 30 item questionnaire with possible answers scored as 1 to 5, with a score of 1 indicating no negative effect, and a score of 5 indicating a constant (all the time) negative effect. Response ranges are from 30 to 150. The outcome will be reported as the median QoL score with standard deviation. | 3 years | 
| Treatment-related Adverse Events ≥ Grade 3 | Toxicity will be assessed as adverse events that are severe or greater (≥ Grade 3), and possibly, probably, or definitely related to mogamulizumab or low dose total skin electron beam therapy (LD TSEBT), and occurring within 12 months of starting treatment. The outcome will be reported as the total number of qualifying events, a number without dispersion. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTCL