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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42782   clinical trials with a EudraCT protocol, of which   7047   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
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    Summary
    EudraCT Number:2017-002544-32
    Sponsor's Protocol Code Number:UCL/15/0515
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-01-26
    Trial 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 number2017-002544-32
    A.3Full title of the trial
    A phase II study of nivolumab monotherapy in patients with relapsed/refractory Hodgkin lymphoma, fit for autologous stem cell transplant, who fail to reach complete metabolic remission after first or second line salvage therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study of nivolumab monotherapy in patients with relapsed/refractory Hodgkin lymphoma fit for autologous stem cell transplant who fail to reach complete metabolic remission after first or second line salvage therapy
    A.3.2Name or abbreviated title of the trial where available
    ANIMATE
    A.4.1Sponsor's protocol code numberUCL/15/0515
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03337919
    A.5.4Other Identifiers
    Name:Funder ReferenceNumber:CA-209-445
    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 SponsorUniversity College London
    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 supportBristol-Myers Squibb Pharmaceuticals Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCRUK & UCL Cancer Trials Centre
    B.5.2Functional name of contact pointOliver Schofield
    B.5.3 Address:
    B.5.3.1Street Address90 Tottenham Court Road
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeW1T 4TJ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number020 7679 9860
    B.5.5Fax number020 7679 9861
    B.5.6E-mailctc.animate@ucl.ac.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 Yes
    D.2.1.1.1Trade name Opdivo
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameOpdivo
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form Concentrate for 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 INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    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 Yes
    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
    Relapsed/refractory Hodgkin lymphoma
    E.1.1.1Medical condition in easily understood language
    Hodgkin lymphoma is a cancer of the lymphatic system due to abnormal lymphocytes. Refractory means not responding to initial treatment. Relapse is where disease returns after initial response.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10020266
    E.1.2Term Hodgkin's disease recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10020267
    E.1.2Term Hodgkin's disease refractory
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether nivolumab, given on its own, can be used effectively to treat patients with Hodgkin lymphoma that has either failed to respond to initial treatment or which has returned after initially responding to treatment, and has not responded fully to salvage chemotherapy. The trial aims to find out how many patients have a negative PET-CT scan after 4-8 cycles of nivolumab treatment.
    E.2.2Secondary objectives of the trial
    To investigate whether patients' disease relapses after nivolumab treatment, and if so, how long this takes to happen.

    To find out how long patients live after nivolumab treatment.

    To find out if patients who have a negative PET-CT scan after nivolumab take longer to relapse than those who have a positive PET-CT scan after nivolumab

    To investigate what side effects patients experience from nivolumab treatment.

    To find out whether it is safe for patients to have a stem cell transplant after nivolumab treatment

    To investigate whether PET scanning is an effective way of checking response to nivolumab treatment

    To look at whether there are blood tests that can be used to monitor response to treatment for Hodgkin lymphoma

    To understand more about the biology of Hodgkin lymphoma, and whether it is possible to predict response to salvage treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria for registration
    • Age 16 or over
    • Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse
    • About to receive, receiving or within 14 days of first 2 cycles of first or second line salvage therapy (4 cycles if receiving treatment with brentuximab vedotin)
    • Fit for autologous stem cell transplantation
    • Written informed consent
    • Willing to comply with the contraceptive requirements of the trial



    Inclusion criteria – trial treatment
    • Has received 2 cycles of first line or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
    • PET positive (Deauville score 4 or 5) after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
    • Fit for further salvage chemotherapy
    • ECOG performance status 0-1
    • Creatinine clearance >30ml/min calculated by Cockroft-Gault formula
    • Bilirubin <1.5 x ULN, ALT/AST <2.5 x ULN
    • Adequate bone marrow function (Hb >80g/l, Platelets >50 x 10^9/l, neutrophils >1.0 x 10^9/l
    E.4Principal exclusion criteria
    Exclusion criteria for registration
    • Nodular lymphocyte predominant Hodgkin lymphoma
    • Women who are pregnant or breastfeeding
    • History of colitis, inflammatory bowel disease or pneumonitis
    • Patients with autoimmune disorders excluding patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy
    • Known history of hepatitis B or C infection
    • Known HIV infection
    • History of allergy (including severe/life threatening skin reaction) to monoclonal antibodies, anaphylaxis or uncontrolled allergy
    • Major surgery within 4 weeks prior to registration
    • Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months
    • Non-haematological malignancy within the past 3 years (some exceptions apply – listed in trial protocol)


    Exclusion criteria for trial treatment
    • Deauville score 1-3 after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)
    • Positive serology for hepatitis B or C (unless due to vaccination)
    • Active infection requiring systemic therapy
    • Ongoing immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone or equivalent per day).
    • Chemo- or radiotherapy or corticosteroids at a dose of more than 10mg/day prednisolone or equivalent within 14 days prior to response PET-CT. NOTE: corticosteroids can be used AFTER a positive PET-CT scan for symptomatic disease but must be weaned to a dose of prednisolone ≤10mg/day or less (or equivalent) at least 7 days prior to starting nivolumab.
    • Treatment with any investigational agent within 28 days prior to planned start of nivolumab
    • Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue
    • Pregnant or breastfeeding women
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab
    E.5.1.1Timepoint(s) of evaluation of this end point
    Response assessed by centrally reviewed PET CT scan after 4 and 8 cycles of nivolumab (approximately 2 & 4 months of treatment).

    Scans are to be performed 11-13 days after trial treatment administration during cycles 4 and 8, as per trial requirements on an approved scanner, and images sent to the UK PET Core Lab at St Thomas' Hospital for expert central review.
    E.5.2Secondary end point(s)
    (1)Progression-free survival at 1 year
    (2)Overall survival at 1 year
    (3)Proportion of patients proceeding to SCT (auto-SCT or allo-SCT)
    (4)Safety & toxicity of nivolumab, particularly autoimmune toxicity
    (5)OS and PFS stratified by partial metabolic response (PMR) versus complete metabolic response (CMR) on FDG-PET
    (6)Transplant-related mortality and rate of serious complications of allogeneic transplant (grade 3-4 graft-vs-host disease, hyperacute graft-vs-host disease and steroid-responsive febrile syndrome)
    (7)Correlate PET positive disease with histological evidence of disease on biopsy to establish biopsy negative PMR rate (subject to patient consent; exploratory)
    (8) Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC (exploratory)
    (9) Evaluate the correlation betweem response to nivolumab and biological parameters e.g. PD-1 expression on Reed-Sternberg cells (exploratory)
    E.5.2.1Timepoint(s) of evaluation of this end point
    (1), (2), (3), (5): assessed at 1 year after completion of trial treatment. Longer term survival follow up will also be presented.
    (4): from start of nivolumab until 5 month post last trial treatment administration; late toxicity during follow up will also be reported.
    (6): from transplant day 0 until day 100 post transplant (patients undergoing allogeneic transplant only)
    (7): following cycle 8 of nivolumab (patients who remain PET positive and consent to repeat biopsy only)
    (8): from start of treatment until end of treatment; based on sequential blood samples.
    (9): exploratory analysis based on archival biopsy material collected after study entry
    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 No
    E.6.4Safety Yes
    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 Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other 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.8.4.1Number of sites anticipated in Member State concerned30
    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
    End of trial will be declared when the last patient treated with nivolumab has completed three years of follow up.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    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 Yes
    F.1.1Number of subjects for this age range: 10
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 10
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 110
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 120
    F.4.2.2In the whole clinical trial 120
    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)
    Trial treatment is of a limited duration (up to 8 cycles) and BMS have committed to supply nivolumab for the duration of the trial. Therefore ANIMATE patients will not require treatment with the study drug beyond the end of the research.

    Patients will receive the local standard of care for their disease as required after the trial ends.
    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 Decision2018-02-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-01
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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