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)

NCT03385226 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UCL/17/00532017-000433-30
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Cutaneous T Cell Lymphoma; Mycosis Fungoides/Sezary Syndrome

Keywords

Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• Overall Response (Global Assessment)

  Overall Response of the combination of pembrolizumab plus radiotherapy

  24 weeks after commencement of pembrolizumab

Secondary Outcomes (7)

• Response

  12 weeks after start of pembrolizumab

• Change in Global Response

  24 weeks after start of pembrolizumab

• Safety and toxicity

  5 months after last dose of pembrolizumab (anticipated 2 years and 5 months after last patient being registered)

• Response Duration

  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 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)

Other Outcomes (8)

• Assessment of changes in the immune status

  24 weeks after start of pembrolizumab

• Analysis of plasma High Mobility Group Box 1 (HMGB-1) isoform levels

  24 weeks after start of pembrolizumab

• Functional analysis of isolated cell populations

  24 weeks after start of pembrolizumab

Study Arms (1)

Pembrolizumab with radiotherapy

EXPERIMENTAL

All patients will receive * single 200mg pembrolizumab IV infusions given 3-weekly until 2 years post study entry, termination of treatment, disease progression or unacceptable toxicity * radiotherapy, 12Gy in 3 fractions

Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

Pembrolizumab DRUG

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.

Also known as: Chemical Abstract Service (CAS) number - 1374853-91-4

Pembrolizumab with radiotherapy

Radiotherapy RADIATION

12Gy in 3 fractions

Pembrolizumab with radiotherapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (11)

University Hospital Birmingham

Birmingham, United Kingdom

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

University Hospital Coventry

Coventry, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Guy's & St Thomas'

London, United Kingdom

Location

The Christie

Manchester, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Southampton University Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• Narducci MG, Tosi A, Frezzolini A, Scala E, Passarelli F, Bonmassar L, Monopoli A, Accetturi MP, Cantonetti M, Antonini Cappellini GC, De Galitiis F, Rosato A, Picozza M, Russo G, D'Atri S. Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab. Front Immunol. 2020 Sep 25;11:579894. doi: 10.3389/fimmu.2020.579894. eCollection 2020.

  PMID: 33072126 DERIVED

MeSH Terms

Conditions

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

Interventions

pembrolizumab; Radiotherapy

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Tim Illidge

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2017
• First Posted: December 28, 2017
• Study Start: January 15, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2025
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (11)