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)

NCT ID: NCT03385226

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-15
• Study Completion Date: 2025-09-30

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.

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).

Conditions

Cutaneous T Cell Lymphoma; Mycosis Fungoides/Sezary Syndrome

Keywords

Relapsed; Refractory

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab with radiotherapy

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

12Gy in 3 fractions

Interventions

Pembrolizumab

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.

Intervention Type: DRUG

Radiotherapy

12Gy in 3 fractions

Intervention Type: RADIATION

Other Intervention Names

Chemical Abstract Service (CAS) number - 1374853-91-4

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Illidge

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Locations

University Hospital Birmingham

Birmingham, , United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

University Hospital Coventry

Coventry, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Guy's & St Thomas'

London, , United Kingdom

The Christie

Manchester, , United Kingdom

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Southampton University Hospital

Southampton, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33072126 (View on PubMed)

Other Identifiers

2017-000433-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UCL/17/0053

Identifier Type: -

Identifier Source: org_study_id