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

NCT03617224 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: STU 032018-018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cutaneous T-Cell Lymphomas

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The highest dose in the regimen is assessed if dose limiting toxicities do not halt escalation.

  1 Year

Secondary Outcomes (4)

• Response to therapy

  4 Years

• Progression-free survival

  4 Years

• Health-related quality of life (HRQOL)

  4 Years

• Dose Limiting Toxicities (DLT)

  4 Years

Study Arms (2)

TSEBT and pembrolizumab

EXPERIMENTAL

Dose regimens are sequential therapy of TSEBT with Pembrolizumab.

Drug: TSEBT and pembrolizumab

Radiation: TSEBT

EXPERIMENTAL

The regimen includes a rule-based "3+3" design for escalating regimen intensity of combined TSEBT and pembrolizumab.

Radiation: TSEBT

Interventions

TSEBT RADIATION

The regimen includes a rule-based "3+3" design for escalating regimen intensity of combined TSEBT and pembrolizumab.

Radiation: TSEBT

TSEBT and pembrolizumab DRUG

Dose regimens are sequential therapy of TSEBT with Pembrolizumab.

TSEBT and pembrolizumab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 6, 2018
• Study Start: July 24, 2018
• Primary Completion: July 24, 2022
• Study Completion: July 24, 2024
• Last Updated: April 22, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)