- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03385226
A Trial Assessing the Effect of Pembrolizumab Combined With Radiotherapy in Patients With Relapsed, Refractory, Specified Stages of Cutaneous T-cell Lymphoma (CTCL) Mycosis Fungoides (MF)/Sezary Syndrome (SS) (PORT)
December 5, 2023 updated by: University College, London
Phase II Trial of Pembrolizumab and Radiotherapy in Cutaneous T-cell Lymphoma
Trial Subjects (patients), will receive single infusions of pembrolizumab every 3 weeks until disease progression or unacceptable toxicity develops.
They will receive radiotherapy at week 12.
Study Overview
Status
Active, not recruiting
Intervention / Treatment
Detailed Description
Trial Subjects (patients) who are deemed eligible for the trial will be administered a single infusion of pembrolizumab (200mg) every 3 weeks.
At week 12, patients will be planned to start radiotherapy at a dose of 12 Gray (Gy) in 3 fractions which will be given concomitantly with pembrolizumab.
Patients who progress on pembrolizumab before week 12 will start radiotherapy as soon as possible after progression.
Following completion of radiotherapy, patients will continue receiving pembrolizumab at 3 weekly intervals for a maximum of 2 years until disease progression or unacceptable toxicity develops.
Patients on pembrolizumab will be seen every 3 weeks until 2 years after study entry, while Patients who progressed/ stopped pembrolizumab will be seen annually for survival/disease status only.
Patients completing 2 years of treatment will then be followed up annually for survival and disease status until the end of trial is declared (2 years after the last patient is registered).
Study Type
Interventional
Enrollment (Actual)
46
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: PORT Trial Coordinator
- Phone Number: +44-2076799860
- Email: ctc.port@ucl.ac.uk
Study Contact Backup
- Name: Jon Teague
- Phone Number: +44-2076799891
- Email: j.teague@ucl.ac.uk
Study Locations
-
-
-
Birmingham, United Kingdom
- University Hospital Birmingham
-
Cardiff, United Kingdom
- Velindre Cancer Centre
-
Coventry, United Kingdom
- University Hospital Coventry
-
Glasgow, United Kingdom
- Beatson West Of Scotland Cancer Centre
-
London, United Kingdom
- Guy's & St Thomas'
-
Manchester, United Kingdom
- The Christie
-
Newcastle, United Kingdom
- Freeman Hospital
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Nottingham, United Kingdom
- Nottingham City Hospital
-
Oxford, United Kingdom
- Churchill Hospital
-
Southampton, United Kingdom
- Southampton University Hospital
-
Wirral, United Kingdom
- Clatterbridge Cancer Centre
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age ≥ 18 years
- Diagnosis of Stage IB-IVB CTCL mycosis fungoides (MF)/Sézary Syndrome (SS)
- Have relapsed, are refractory or progressed after at least 1 systemic therapy
- Skin biopsy at the time of or within 6 months prior to study entry
- Patients must have a total mSWAT (modified Severity Weighted Assessment Tool) score of ≥10 OR have 2 or more measurable tumours of any size. Of this area: there should be at least 1 cutaneous lesion (MF) or a defined area of involved skin (erythrodermic MF or SS) which is an appropriate target for palliative radiotherapy. There should be an area of skin involved by measurable Mycosis Fungoides/SS that will not be irradiated (To assess the abscopal effect of radiotherapy)
- Have a minimum wash-out and adverse event (AE) recovery period from previous treatments (e.g. topical therapy, phototherapy, local radiotherapy, monoclonal antibody, systemic cytotoxic anticancer treatment or other novel agents) prior to the first dose of pembrolizumab
- Have ECOG performance status of 0 or 1
- Life expectancy of at least 6 months
- Demonstrate adequate organ function
- Female patients of childbearing potential must have a negative urine or serum pregnancy test at pre-registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Willing to comply with the contraception requirements
Written informed consent
•Exclusion Criteria:
- Received chemotherapy or targeted small molecule therapy within 4 weeks prior to study entry or has not recovered from adverse events due to agents administered >4 weeks earlier (except patients with ≤ grade 2 neuropathy)
- Is currently or has participated in an IMP or device study within 4 weeks prior to the first dose of pembrolizumab
- Received any other monoclonal antibody within 15 weeks prior to the first dose of pembrolizumab or has not recovered (≤ grade 1 or to baseline level) from adverse events due to agents administered >4 weeks earlier. The exception to this is alemtuzumab which should not have been administered in the previous 12 weeks
- Additional malignancy that is progressing or requires active treatment
- Patients with known central nervous system (CNS) involvement with lymphoma
- Hypersensitivity to pembrolizumab or its excipients
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Stable use of corticosteroids (at a dose no higher than 10mg prednisolone per day over the preceding 4 weeks) is allowed
- Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive therapy
- Current or prior use of immunosuppressive therapy within 7 days prior to start of treatment except the following: intranasal, inhaled, topical steroids or local steroid injections (eg. Intra-articular injection); systemic corticosteroids at physiologic doses (10mg/day or less of prednisolone or equivalent)
- Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
- Has known history of, or any evidence of active, non-infectious pneumonitis
- History of other pulmonary disease such as interstitial lung disease, emphysema or chronic obstructive pulmonary disease
- Is pregnant or breastfeeding
- Has a known history of active TB
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with the subject's participation for the full duration of the trial or to participate in the trial is not in the patient's best interest, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with the requirements of the trial
- Has a known history of HIV
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days prior to the planned start of study medication
- Patients who have previously received a solid organ transplant
- Patients who have previously received any allogeneic transplantation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab with radiotherapy
All patients will receive
|
Pembrolizumab is a humanised monoclonal antibody which targets the programmed cell death 1 (PD-1) receptor.
It blocks a protective mechanism on cancer cells, and allows the immune system to destroy those cancer cells.
Other Names:
12Gy in 3 fractions
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response (Global Assessment)
Time Frame: 24 weeks after commencement of pembrolizumab
|
Overall Response of the combination of pembrolizumab plus radiotherapy
|
24 weeks after commencement of pembrolizumab
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response
Time Frame: 12 weeks after start of pembrolizumab
|
Response at the 5th infusion of pembrolizumab, typically 12 weeks after start of treatment
|
12 weeks after start of pembrolizumab
|
Change in Global Response
Time Frame: 24 weeks after start of pembrolizumab
|
Change in Global Response from the 5th infusion to the 9th infusion, typically from week 12 to week 24
|
24 weeks after start of pembrolizumab
|
Safety and toxicity
Time Frame: 5 months after last dose of pembrolizumab (anticipated 2 years and 5 months after last patient being registered)
|
Number & Percentage of patients who suffer grade 3 or 4 toxicity
|
5 months after last dose of pembrolizumab (anticipated 2 years and 5 months after last patient being registered)
|
Response Duration
Time Frame: Time from date of first confirmed response to the first date of diagnosis of progressive disease or death from any cause (anticipated by 2 years and 5 months after the last patient being registered)
|
Duration of tumour response
|
Time from date of first confirmed response to the first date of diagnosis of progressive disease or death from any cause (anticipated by 2 years and 5 months after the last patient being registered)
|
Progression Free Survival
Time Frame: Time from date of registration to the date of first progression or death from any cause ((anticipated by 2 years and 5 months after the last patient being registered)
|
Disease progression or death
|
Time from date of registration to the date of first progression or death from any cause ((anticipated by 2 years and 5 months after the last patient being registered)
|
Overall Survival
Time Frame: Time from date of registration to the date of death from any cause ((anticipated by 2 years and 5 months after the last patient being registered)
|
Death
|
Time from date of registration to the date of death from any cause ((anticipated by 2 years and 5 months after the last patient being registered)
|
Number of patients achieving abscopal effect
Time Frame: Through study completion, 2 years post last patient being registered
|
Through study completion, 2 years post last patient being registered
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of changes in the immune status
Time Frame: 24 weeks after start of pembrolizumab
|
Peripheral blood mononuclear cell phenotyping
|
24 weeks after start of pembrolizumab
|
Analysis of plasma High Mobility Group Box 1 (HMGB-1) isoform levels
Time Frame: 24 weeks after start of pembrolizumab
|
Peripheral blood mononuclear cell phenotyping
|
24 weeks after start of pembrolizumab
|
Functional analysis of isolated cell populations
Time Frame: 24 weeks after start of pembrolizumab
|
Peripheral blood mononuclear cell phenotyping
|
24 weeks after start of pembrolizumab
|
Assessment of diversity and clonality of T cell clones
Time Frame: 24 weeks after start of pembrolizumab
|
DNA extraction for T cell receptor sequencing
|
24 weeks after start of pembrolizumab
|
Evaluation of immune signatures for responders and non-responders
Time Frame: 24 weeks after start of pembrolizumab
|
Peripheral blood mononuclear cell phenotyping
|
24 weeks after start of pembrolizumab
|
Epitope screening for tumour infiltrating lymphocyte specific neo-antigens
Time Frame: 24 weeks after start of pembrolizumab
|
Peripheral blood mononuclear cell phenotyping
|
24 weeks after start of pembrolizumab
|
Immunohistochemical analysis of expression of immunological checkpoints
Time Frame: At baseline
|
Assessment of PD-L1 expression
|
At baseline
|
Investigation of the baseline tumour immune microenvironment
Time Frame: At baseline
|
Immune cell infiltration
|
At baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Tim Illidge, University of Manchester
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 15, 2019
Primary Completion (Actual)
September 1, 2023
Study Completion (Estimated)
September 1, 2024
Study Registration Dates
First Submitted
December 12, 2017
First Submitted That Met QC Criteria
December 27, 2017
First Posted (Actual)
December 28, 2017
Study Record Updates
Last Update Posted (Estimated)
December 6, 2023
Last Update Submitted That Met QC Criteria
December 5, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Disease
- Bacterial Infections and Mycoses
- Lymphoma
- Syndrome
- Mycoses
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Lymphoma, T-Cell, Cutaneous
- Mycosis Fungoides
- Sezary Syndrome
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- UCL/17/0053
- 2017-000433-30 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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