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

Phase I Trial of Pembrolizumab and Total Skin Electron Beam Radiotherapy in Mycosis Fungoides and Sézary Syndrome

NCT03617224•University of Texas Southwestern Medical Center

Summary

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.

Eligibility

Age

18 - 120 years

Sex

ALL

Healthy Volunteers

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
+12 more criteria

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.
+10 more criteria

Locations (1)

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Key Dates

Start Date

July 24, 2018

Primary Completion Date

July 24, 2022

Completion Date

July 24, 2024

Last Updated

April 22, 2020

Conditions

Cutaneous T-Cell Lymphomas

Interventions

TSEBT

RADIATION

TSEBT and pembrolizumab

DRUG