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Cutaneous T-Cell LymphomasPhase 1NCT03617224

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

A Phase 1 study testing TSEBT and TSEBT and pembrolizumab in people with Cutaneous T-Cell Lymphomas, run by University of Texas Southwestern Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Cutaneous T-Cell Lymphomas
What is being tested?
TSEBT and TSEBT and pembrolizumab
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
24 Jul 2018to 24 Jul 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

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

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.
Read the 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.

Being tested
TSEBT, TSEBT and pembrolizumab
Keywords
Mycosis Fungoides (MF), Sezary Syndrome (SS), Pembrolizumab, Total Skin Electron Beam Therapy (TSEBT)
Medical subject headings
Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Sezary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TSEBTRadiation

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

  • TSEBT and pembrolizumabDrug

    Dose regimens are sequential therapy of TSEBT with Pembrolizumab.

Study groups in NCT03617224
Study groupRoleWhat they receive
TSEBT and pembrolizumabExperimentalDose regimens are sequential therapy of TSEBT with Pembrolizumab.
Receives: Drug: TSEBT and pembrolizumab
Radiation: TSEBTExperimentalThe regimen includes a rule-based "3+3" design for escalating regimen intensity of combined TSEBT and pembrolizumab.
Receives: Radiation: TSEBT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

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

    Measured: 1 Year

Secondary outcomes (4)

  1. Response to therapy

    The response to therapy is measured from overall response criteria from initiation of any therapy.

    Measured: 4 Years

  2. Progression-free survival

    Progression-free survival is measured without the development of new metastasis.

    Measured: 4 Years

  3. Health-related quality of life (HRQOL)

    HRQOL's are measured using the Skindex-29. The higher the number better the quality of life.

    Measured: 4 Years

  4. Dose Limiting Toxicities (DLT)

    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).

    Measured: 4 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2018
  2. Study start24 Jul 2018
  3. Primary completion24 Jul 2022 (estimated)
  4. Study completion24 Jul 2024 (estimated)

Why it stopped: Unable to enroll patients that met enrollment criteria.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03617224
Sponsor's protocol ID
STU 032018-018
Status last verified
Apr 2020
First submitted
27 Jul 2018
Last updated
22 Apr 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TSEBT and TSEBT and pembrolizumab in people with Cutaneous T-Cell Lymphomas, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 1 Year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03617224.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2020.

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