Clinical Trials /

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

NCT04256018

Description:

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.

Related Conditions:
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mogamulizumab + Low-Dose Total Skin Electron Beam Tx in Mycosis Fungoides & Sézary Syndrome
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: IRB-53490
  • SECONDARY ID: LYMNHL0155
  • NCT ID: NCT04256018

Conditions

  • Sezary Syndrome
  • Mycosis Fungoides

Interventions

DrugSynonymsArms
MogamulizumabLD TSEBT

Purpose

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

      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
    

Trial Arms

NameTypeDescriptionInterventions
LD TSEBTExperimentalMogamulizumab 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)
  • Mogamulizumab

Eligibility Criteria

        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

          -  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/cutaneous T-cell lymphoma (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

          -  Current evidence of large cell transformed disease

             _ Concomitant corticosteroid use. (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
             entry)

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:6 months
Safety Issue:
Description:Response to treatment will be assessed as the number and proportion of participants who achieve either a complete response (CR) or partial response (PR), and maintain a response for 6 months. 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.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:4, 9 and 12 months
Safety Issue:
Description:Overall Response to treatment will be assessed as the number and proportion of participants who achieve either a complete response (CR) or partial response (PR), and maintain a response for 4, 9, and 12 months. The outcome is reported as numbers without dispersion.
Measure:Time-to-Next Significant Treatment (TTNT)
Time Frame:3 years
Safety Issue:
Description: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 with standard deviation.
Measure:Progression free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:Progression free survival (PFS) will be assessed as the number and proportion of patients who achieve a clinical response and remain alive at 12 months after initiation of treatment. The outcome is reported as a number without dispersion.
Measure:Duration of response (DOR)
Time Frame:12 months
Safety Issue:
Description: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.
Measure:Patient reported Quality of Life (QoL)
Time Frame:3 years
Safety Issue:
Description: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.
Measure:Treatment-related Adverse Events ≥ Grade 3
Time Frame:12 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Stanford University

Last Updated

February 4, 2020