E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous T cell lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Cutaneous T cell Lymphoma is a cancer that affects the skin (Cutaneous means related or affecting the skin). The cancer originates from T cell lymphocytes,a type of white blood cells. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011677 |
E.1.2 | Term | Cutaneous T-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Would the addition of radiotherapy to pembrolizumab improve the response to treatment and is it safe to give? |
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E.2.2 | Secondary objectives of the trial |
- What is the response to pembrolizumab prior to giving radiotherapy - Change in Global response from radiotherapy to the 9th infusion - Best Overall response - Shrinkage of any other tumours where radiotherapy was not directly targeting (abscopal effect) - Duration of response - Time to next treatment - Side effect of trial treatment, and how many patients experienced them? - What is the time from study entry to progression or death (Progression-free survival) - What is the time from study entry to death from any cause (Overall survival) - Investigation of the immune biomarkers of response to the trial treatment - Is there a change in quality of life from study to end of treatment?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: o 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 (see radiotherapy section 8.3.2 for protocol defined min/max irradiated area)
o 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, as detailed in section 6.2.1 of the trial protocol -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 -Willing to comply with the contraception requirements -Written informed consent |
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E.4 | Principal 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. -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 (see section 6.2.2 of the trial protocol) -Patients who have previously received a solid organ transplant -Patients who have previously received any allogeneic transplantation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumour response rate at infusion 9, typically 24 weeks after the first dose of pembrolizumab |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be fully staged (TNMB) within 4 weeks prior to study entry. This staging at ‘screening’ will be used as baseline TNMB for comparison and future Global Response Assessment at the 9th pembrolizumab infusion, typically at 24 weeks. |
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E.5.2 | Secondary end point(s) |
1- Response prior to delivery of radiotherapy 2- Change in Global Response from the time of radiotherapy to the 9th infusion 3- Best overall response 4- Abscopal effect (measured by regression of pre-defined lesions which have not been irradiated) 5- Duration of response 6- Time to next treatment 7- Safety and toxicity 8- Progression-free survival 9- Overall survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Global assessment at the time of radiotherapy 2,3,4,5 - At the time of radiotherapy and at infusions 9 and 13 (typically at 12, 24 and 36 weeks respectively), and at the end of pembrolizumab treatment 6- At infusions 6, 7, 8 and 9 (typically at weeks 15, 18, 21 and 24), then for patients on pembrolizumab every 3 weeks until up to 2 years after study entry 7- Every 3 weeks until up to 2 years and 5 months after study entry 8- Progression or death from any cause 9- Death from any cause |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be when the last patient has their 2 year follow up visit or completed the follow up for safety monitoring (whichever occurs later) (i.e. 2 years and 5 months if the last patient completes 2 years of pembrolizumab treatment and is then followed up for 5 months for safety) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 2 |