Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-001071-20
    Sponsor's Protocol Code Number:CFTSp034
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-09-09
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2013-001071-20
    A.3Full title of the trial
    A Randomised Phase II Study in Metastatic Melanoma to Evaluate the Efficacy of Adoptive Cellular Therapy with Tumour Infiltrating Lymphocytes (TIL) and Assessment of High versus Low Dose Interleukin-2
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomised, Phase II study in metastatic melanoma to evaluate the effectiveness of adoptive cellular therapy with Tumour Infiltrating Lymphocytes (TIL) and assessment of High Dose Intereukin-2 versus Low-Dose Interleukin-2.
    A.3.2Name or abbreviated title of the trial where available
    METILDA
    A.4.1Sponsor's protocol code numberCFTSp034
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorThe Christie NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNational Institute of Health Research FP7
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMAHSC-CTU, The Christie NHS Foundation Trust
    B.5.2Functional name of contact pointIan Emerson
    B.5.3 Address:
    B.5.3.1Street Address550 Wilmslow Road
    B.5.3.2Town/ cityManchester
    B.5.3.3Post codeM20 4BX
    B.5.4Telephone number01619187443
    B.5.6E-mailian.emerson@christie.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTumour Infiltrating Lymphocytes (TIL)
    D.3.2Product code Tumour Infiltrating Lymphocytes (TIL)
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTumour Infiltrating Lymphocytes (TIL)
    D.3.9.3Other descriptive nameTILs
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5x10E9 to 2x10E11
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Malignant Melanoma
    E.1.1.1Medical condition in easily understood language
    Skin cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level LLT
    E.1.2Classification code 10027481
    E.1.2Term Metastatic melanoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the response rate of patients with metastatic melanoma to either standard TIL therapy treatment with high-dose interleukin-2 (HD-IL2) or TIL treatment with low dose interleukin-2 (LD-IL2). To evaluate to feasibility and tolerability of TIL therapy with HD-IL2 versus LD-IL2.
    E.2.2Secondary objectives of the trial
    Secondary Endpoints
    1. Evaluation of Progression Free Survival.
    2. Evaluation of the duration of response.
    3. Assessment of Overall Survival.

    Exploratory Endpoints
    1. Examination of potential tumour related or immunological biomarkers of response facilitate better patient selection in the future.
    2. Evaluation of response rate by immune related Response Criteria (irRC).
    3. Evaluation of TIL harvest process.
    4. Assessment of the cost of treatment.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria for TIL Harvest:
    • Patients must have histologically confirmed malignant melanoma of cutaneous origin.
    • They must have resectable metastatic lesion(s) of at least 2cm in total diameter.
    • They must be likely to fulfil the full criteria for TIL therapy at a future date.
    • The must give full written informed consent to the surgical procedure and the TIL harvest/storage.

    Inclusion Criteria for TIL Therapy
    • Patients must have histologically confirmed malignant melanoma of cutaneous origin with confirmed evidence of progressive metastatic disease and to have failed / refused standard therapies.
    • Patients may enter if they have previously had TIL (successfully) harvested and stored at the Manchester Cell Therapy Unit.
    • There must be measurable / evaluable disease.
    • Patients may have had any previous systemic therapies including anti-CTLA4 (Ipilimumab) agent provided they are otherwise fit for treatment.
    • Age equal to or greater than 18 years.
    • World Health Organisation (WHO) performance status of 0 or 1.
    • Life expectancy >3months.
    • LVEF > 50% as measured by ECHO/MUGA and satisfactory stress ECHO (if over 60 or had previous cardiotoxic therapy).
    Haematological and biochemical indices:
    - Haemoglobin (Hb), ≥ 9.0 g/L
    - Neutrophils, ≥ 1.0 x 109/L
    - Platelets (Plts), ≥ 100 x 109/L
    Any of the following abnormal baseline liver function tests:
    serum bilirubin, ≤ 1.5 x ULN
    - alanine aminotransferase (ALT) and/or
    aspartate aminotransferase (AST) and/or
    alkaline phosphatase (ALP) , ≤ 5 x ULN
    - Serum creatinine, ≤ 0.15 mmol/L
    • Female patients of child-bearing potential must have a negative serum or urine pregnancy test prior treatment and agree to use appropriate medically approved contraceptive precautions for four weeks prior to entering the trial, during the trial and for six months afterwards.
    • Male patients must agree to use barrier method contraception during the TIL treatment and for six months afterwards.
    • Full written informed consent
    E.4Principal exclusion criteria
    Exclusions to TIL Harvest are:
    • Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
    • Previous allogeneic transplant.
    • Patient with ocular/mucosal (or any non-cutaneous primary site) melanoma.
    • Patients who are high medical risks because of non-malignant systemic disease, including those with, uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which in the lead clinicians opinion would not make the patient a good candidate for this therapy.
    • Prior history of malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
    • Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
    • History of systemic autoimmune disease which could be life-threatening if reactivation occurred (for example hypothyroidism would be permissible, prior rheumatoid arthritis or SLE would not).
    • Patients who are likely to require long-term systemic steroids or other
    • Radiotherapy to >25% skeleton.

    Exclusion criteria for TIL Therapy
    • Those receiving radiotherapy, targeted therapy, immunotherapy, systemic steroids, or chemotherapy during the previous four weeks (six weeks for nitrosoureas and Mitomycin-C) prior to treatment or during the course of the treatment.
    • All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities, which an investigator considers should not exclude the patient. For patients who had severe colitis (grade 3 / 4) on Ipilimumab (or similar therapy), this must be confirmed as resolved by colonoscopy.
    • Previous radiotherapy treatment to the resectable metastatic site(s) within 1 year and no other suitable metastatic sites.
    • Participation in any other clinical trial within the previous 30 days or during the course of this treatment.
    • Previous allogeneic transplant.
    • Patient with ocular/mucosal (or any non-cutaneous primary site) melanoma.
    • Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or Class III or IV AHA criteria for heart disease (see Appendix 6)
    • Patients who are high medical risks because of non-malignant systemic disease, including those with, uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which in the lead clinicians opinion would not make the patient a good candidate for this therapy.
    • Evidence of active infection
    • Prior history of malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
    • Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
    • History of systemic autoimmune disease which could be life-threatening if reactivation occurred (for example hypothyroidism would be permissible, prior rheumatoid arthritis or SLE would not).
    • Patients with currently more than 3 brain metastases.
    • Patients with symptomatic brain metastasis measuring more than 10mm in diameter or evidence of significant surrounding oedema on MRI will not be eligible until after treatment demonstrating no clinical or radiologic CNS progression for at least 2 months. Patient must be able to wean off any steroid use 3 weeks before treatment commencement.
    • Patients who are likely to require long-term systemic steroids or other immunosuppressive therapy.
    • Pregnant and lactating women.
    • Radiotherapy to >25% skeleton.
    E.5 End points
    E.5.1Primary end point(s)
    1) To evaluate the anti-tumour activities of TIL therapy with High Dose Interleukin2 (HD-IL2) versus Low Dose Interleukin2 (LD-IL2), by assessing the 3 month response to therapy according to anti-tumour activities and response rates by CT scan, using RECIST v1.1.

    2) Evaluation of the feasibility and tolerability of TIL therapy with HD-IL2 versus LD-IL2. Feasibility will be assessed in terms of proportion of patients who undergo full therapy in both arms. Tolerability will be assessed according to CTCAE v4.0 grading of toxicities experienced.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Feasability will be assessed for all participants at the point at which they complete their study treatment.

    Tolorability will be assessed for all participants until the time point at which they come off study. However, all participants will be followed up post study until the participant is deceased as this is an ATIMP clinical trial.
    E.5.2Secondary end point(s)
    1) Evaluation of the progression free survival. This is defined as the time interval between the treatment starting date and the documented date of disease progression or death, whichever occurs first. For an alive and progression free patient, progression free survival is censored at the last follow-up date when the participant is documented to be progression free.

    2) Evaluation of the duration of response. Assessing anti-tumour activity using Immune-related Response Criteria. Using CT scans, this incorporates measurable new lesions that may have developed on-study, providing an assessment that includes both baseline and new lesions. The tumour assessment performed during screening will serve as baseline for determination of tumour response using Immune-related Response Criteria.

    3) Assessment of overall survival. This is the time interval between the treatment start date and the documented date of death. For a surviving participant, overall survival is recorded up to the last follow-up date when the participant is documented to be alive.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) The documented date of disease progression or death, whichever occurs first, or the last follow-up date when the participant is documented to be progression free.

    2) The CT scan timepoint at which the nadir of total tumour burden was recorded.

    3) Documented date of death, or last date participant is documented to be alive.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state90
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 90
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Not applicable as participants will be given one cycle of treatment only. The participants will be followed-up for life.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-11-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-23
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2015-09-15
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon May 06 22:33:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA