Clinical Trials /

Pembrolizumab and Total Skin Electron Beam Radiotherapy in Mycosis Fungoides and Sézary Syndrome

NCT03617224

Description:

Hypothesis: Addition of low dose TSEBT to debulk MF/SS either before or during checkpoint blockade with anti-PD-1 pembrolizumab monoclonal antibody therapy will be safe and well tolerated. Primary Objective: • To determine the maximum tolerated dose (MTD) for the combination of total skin electron beam therapy (TSEBT) and pembrolizumab regimen. Secondary Objectives: - To determine the preliminary efficacy of the combination of TSEBT with pembrolizumab. - To determine the impact on patient-reported health-related quality of life outcomes.

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

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Total Skin Electron Beam Radiotherapy in Mycosis Fungoides and Sézary Syndrome
  • Official Title: Phase I Trial of Pembrolizumab and Total Skin Electron Beam Radiotherapy in Mycosis Fungoides and Sézary Syndrome

Clinical Trial IDs

  • ORG STUDY ID: STU 032018-018
  • NCT ID: NCT03617224

Conditions

  • Cutaneous T-Cell Lymphomas

Purpose

Hypothesis: Addition of low dose TSEBT to debulk MF/SS either before or during checkpoint blockade with anti-PD-1 pembrolizumab monoclonal antibody therapy will be safe and well tolerated. Primary Objective: • To determine the maximum tolerated dose (MTD) for the combination of total skin electron beam therapy (TSEBT) and pembrolizumab regimen. Secondary Objectives: - To determine the preliminary efficacy of the combination of TSEBT with pembrolizumab. - To determine the impact on patient-reported health-related quality of life outcomes.

Detailed Description

      This is a single center phase I clinical trial assessing the safety of combination therapy of
      TSEBT and pembrolizumab for treatment of Stage IB-IV relapsed/refractory MF and SS.

      Primary Endpoint:

      • Primary endpoint will be maximum tolerated dose (MTD).

      Secondary Endpoints:

        -  Efficacy of the combination of TSEBT with pembrolizumab therapy is measured.

        -  CTCAE v4.0 toxicity beyond the 30 day period following the second therapy in the
           combination protocol treatment and up to 30 days following last dose of pembrolizumab.

        -  Skindex-29 patient-reported HRQOL survey.

      Sample Size and Accrual: 18 patients will be enrolled.

      Statistical Analysis: Time to event will be estimated using the Kaplan-Meier approach along
      with the 95% confidence interval.
    

Trial Arms

NameTypeDescriptionInterventions
TSEBT and pembrolizumabExperimentalDose regimens are sequential therapy of TSEBT with Pembrolizumab.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Biopsy confirmed Mycosis Fungoides or Sézary Syndrome
    
              -  Stage IB-IV by ISCL/EORTC 2007 Revision Staging (See Appendix Section 13.3). Maximal
                 stage since diagnosis will determine eligibility.
    
              -  Failed or intolerant to at least one prior line of systemic therapy
    
              -  Life expectancy > 6 months
    
              -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 and able to stand for
                 TSEBT
    
              -  Baseline measurable disease by the mSWAT criteria
    
              -  Acceptable baseline laboratories:
    
                   -  Leukocytes ≥ 2,000/mcL
    
                   -  Absolute neutrophil count ≥ 1,500/mcL
    
                   -  Platelets ≥ 100,000/mcl
    
                   -  Hemoglobin ≥ 9g/dL
    
                   -  Total bilirubin ≤ 1.5 X institutional upper limit of normal
    
                   -  AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
    
                   -  INR/PT ≤ 1.5 X institutional upper limit of normal (*unless on anticoagulation
                      therapy and therapeutic)
    
                   -  Serum creatinine ≤ 1.5 X institutional upper limit normal OR ≥ 60 mL/min
                      calculated creatinine clearance ≥60 mL/min for subject
    
              -  Women of child-bearing potential and men must agree to use adequate contraception
                 (hormonal or barrier method of birth control; abstinence) prior to study entry, for
                 the duration of study participation, and for 90 days following completion of therapy.
                 Should a woman become pregnant or suspect she is pregnant while participating in this
                 study, she should inform her treating physician immediately.
    
              -  A female of child-bearing potential is any woman (regardless of sexual orientation,
                 having undergone a tubal ligation, or remaining celibate by choice) who meets the
                 following criteria:
    
                   -  Has not undergone a hysterectomy or bilateral oophorectomy; or
    
                   -  Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
                      has had menses at any time in the preceding 12 consecutive months).
    
              -  Ability to understand and the willingness to sign a written informed consent.
    
              -  Patient must provide tissue biopsy (punch) of skin at baseline (pre-study treatment),
                 following 3 cycles of pembrolizumab, 1 month following end of TSEBT, at clinical event
                 of progression, at end of treatment (unless at same time as progression triggered
                 biopsy). Optional biopsy can be taken every 3 cycles of pembrolizumab and at time of
                 initial response to pembrolizumab.
    
              -  Must be a candidate for TSEBT
    
            Exclusion Criteria:
    
              -  Subjects who have had prior TSEBT (prior focal radiotherapy is allowed).
    
              -  Subjects who have had systemic cytotoxic anticancer agents or radiotherapy within 2
                 weeks prior to entering the study or those who have not in the opinion of the treating
                 physician recovered from adverse events due to agents administered more than 2 weeks
                 earlier.
    
              -  Subjects who have received the following prior therapies:
    
              -  Alemtuzumab within the past 8 weeks
    
              -  Retinoids, interferons, Vorinostat, Romidepsin, oral corticosteroids (except
                 physiologic replacement dose or topicals) within the past 2 weeks
    
              -  Phototherapy within the past 4 weeks
    
              -  Topical therapies including retinoids, nitrogen mustards and Imiquimod within the past
                 week
    
              -  Patients may not have received systemic steroid therapy or other form of
                 immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
    
              -  Subjects may not be receiving any other investigational agents during the study or for
                 within 4 weeks of registration.
    
              -  Subjects with known brain metastases should be excluded from this clinical trial
                 because of their poor prognosis and because they often develop progressive neurologic
                 dysfunction that would confound the evaluation of neurologic and other adverse events.
    
              -  Subjects with known history of immunodeficiency or severe autoimmune disease requiring
                 systemic immunosuppressive agents or severe connective tissue diseases (i.e. systemic
                 scleroderma) or DNA damage repair deficiency syndromes that are known to pre-dispose
                 to excess DNA damage hypersensitivity from ionizing radiation will be excluded from
                 the study.
    
              -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, active hepatitis B or C, history of pneumonitis requiring steroids, or
                 psychiatric illness/social situations that would limit compliance with study
                 requirements.
    
              -  Subjects must not have received a recent live vaccine within 30 days of treatment.
    
              -  Subjects must not be pregnant or nursing due to the potential for congenital
                 abnormalities and the potential of this regimen to harm nursing infants.
    
              -  Patients with history of hypersensitivity to monoclonal antibodies.
    
              -  History of prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to MK-3475 (pembrolizumab)
    
              -  Patients may not have an additional known malignancy requiring active treatment or
                 which his progressing, excluding non-melanoma skin cancer or in situ cervical cancer
                 which has undergone potentially curative therapy.
    
              -  Known human T-lymphotropic virus type 1 (HTLV) infection
    
              -  History of non-infectious pneumonitis requiring steroids
          
    Maximum Eligible Age:120 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximum Tolerated Dose (MTD)
    Time Frame:1 Year
    Safety Issue:
    Description:The highest dose in the regimen is assessed if dose limiting toxicities do not halt escalation.

    Secondary Outcome Measures

    Measure:Response to therapy
    Time Frame:4 Years
    Safety Issue:
    Description:The response to therapy is measured from overall response criteria from initiation of any therapy.
    Measure:Progression-free survival
    Time Frame:4 Years
    Safety Issue:
    Description:Progression-free survival is measured without the development of new metastasis.
    Measure:Health-related quality of life (HRQOL)
    Time Frame:4 Years
    Safety Issue:
    Description:HRQOL's are measured using the Skindex-29. The higher the number better the quality of life.
    Measure:Dose Limiting Toxicities (DLT)
    Time Frame:4 Years
    Safety Issue:
    Description:Severity or Toxicity will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. Dose adjustments should be made according to the system showing the greatest degree of toxicity. The consequences of toxicity should all be graded 1-5 according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 occurring prior to 270 days from the start of protocol treatment. CTCAE V4.0 along with grades 1-5 is provided in the link for reference (https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06 14_QuickReference_8.5x11.pdf).

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Texas Southwestern Medical Center

    Trial Keywords

    • Mycosis Fungoides (MF), Sezary Syndrome (SS), Pembrolizumab, Total Skin Electron Beam Therapy (TSEBT)

    Last Updated

    April 10, 2019