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    Summary
    EudraCT Number:2012-005010-19
    Sponsor's Protocol Code Number:MPD-RC114
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-04-16
    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 number2012-005010-19
    A.3Full title of the trial
    Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) with Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Exploring the potential of adding the drug Ruxolitinib to the standard reduced intensity (lower strength) chemotherapy regimen prior to bone marrow transplant in patients with myelofibrosis.
    A.3.2Name or abbreviated title of the trial where available
    MPD-RC 114
    A.4.1Sponsor's protocol code numberMPD-RC114
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01790295
    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 SponsorConsorzio Mario Negri Sud
    B.1.3.4CountryItaly
    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 Cancer Institute
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportLeukaemia & Lymphoma Research
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationWhetherall Institute of Molecular Medicine
    B.5.2Functional name of contact pointDr Lee Potiphar
    B.5.3 Address:
    B.5.3.1Street AddressJohn Radcliffe Hospital
    B.5.3.2Town/ cityHeadington
    B.5.3.3Post codeOX3 9DS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01865 857947
    B.5.5Fax number01865 222500
    B.5.6E-maillee.potiphar@ndcls.ox.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 Jakavi
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/08/572 and EU/3/09/620
    D.3 Description of the IMP
    D.3.1Product nameRuxolitinib (INC424)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPNasogastric use (Noncurrent)
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRuxolitnib
    D.3.9.1CAS number 1092939-17-7
    D.3.9.2Current sponsor codeINC424
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5 to 25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) 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 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
    Primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF)
    E.1.1.1Medical condition in easily understood language
    MF is a form of bone marrow cancer in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10028537
    E.1.2Term Myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary aim of this study is to evaluate whether or not combining Ruxolitinib with a RIC regimen is likely to produce success after bone marrow transplantation, and thereby determine if it is a suitable treatment for patients with myelofibrosis. A RIC regimen is the chemotherapy treatment used to prepare patients for a bone marrow transplant.

    Success in this trial is defined as the patient being alive, and without graft failure (when normal bone marrow function does not come back after a stem cell transplant) 100 days after the transplant. Two patient groups will be assessed independently: those who receive a related donor transplant (from a family member) and in those who receive an unrelated donor transplant, as the risk of the transplant varies markedly according to the donor type.
    E.2.2Secondary objectives of the trial
    1. The time for blood counts to recover after the transplant
    2. Number of deaths due to treatment at 100 days and 1-year after treatment
    3. Acute and chronic Graft versus Host Disease (GvHD) at 1-year. GvHD is caused by new donor cells treating the body as 'foreign' and launching an attack against it. 4. Chimerism studies at 30, 60 and 100 days post transplant. Chimerism studies look at who the cells in the bone marrow are originally from - either the donor or the recipient.
    5. Remission (lack of disease activity) status at day 100, and 6 and 12 months post transplant
    6. Disease return / worsening at 1-year post transplant
    7. Survival without disease worsening at 1-year
    8. Overall Survival at 1-year
    9. Impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life
    10. Measurements of the levels of activity of genes (basic units of inheritance) and signalling molecules (used to send messages in the body's cells) prior to start of Ruxo
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    The sub study: Correlative Biomarker Study for MPD-RC Treatment Studies in the Philadelphia Chromosome Negative Myeloproliferative Neoplasms (MPN)-MPD-RC 107 Version '4' dated 2/5/2013. Please note: the 107 sub-study will be submitted alongside this 114 study.
    E.3Principal inclusion criteria
    1. Documented diagnosis of primary myelofibrosis according to WHO (World Health Organisation) criteria or either post PV (polycythemia vera) myelofibrosis or post ET (essential thrombocythemia) myelofibrosis as per IWG-MRT (International Working Group-Myeloproliferative Neoplasms Research and Treatment) criteria
    2. Age 18–70 years
    3. Intermediate- 2 / high-risk disease as per Dynamic International Prognostic Scoring System (DIPSS) criteria
    OR
    Intermediate- 1 risk disease with one of the following additional unfavourable features known to impact upon survival, adversely
    a. Red cell transfusion dependency
    b. Unfavourable Karyotype
    c. Platelet count less than 100 x 109/L
    4. Blasts in Peripheral Blood and Bone Marrow less than 20% prior to study enrolment
    5. Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched)
    6. Able to give informed written consent
    7. ECOG Performance status of 0-2
    8. Life expectancy greater than 3 months
    9. Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrolment and recovered from all toxicities*
    10. Adequate organ function:
    • Adequate renal function – creatinine less than 1.5 x Institutional Upper Limit of Normal (IULN)
    • Adequate hepatic function – Aspartate Aminotransferase / Alanine Aminotransferase (AST/ALT) less than 2.5 x IULN, Total Bilirubin less than 1.5 x IULN
    • Adequate hematopoietic function – Platelet greater than or equal to 50 x 109/L and Absolute Neutrophil Count greater than or equal 1.0 x 109/L
    • Left Ventricular Ejection Factor (LVEF) greater than 40% (Multiple Gated Acquisition Scan or echocardiogram) normal per institutional standard
    • Adequate pulmonary function with Diffusing capacity of Lung Carbon Dioxide (DLCO) greater than 50%
    * A patient who has been on stable dose of Ruxolitinib and has received treatment less than or equal to 6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (greater than 5cm increase in spleen size from the lowest point termed 'nadir').
    E.4Principal exclusion criteria
    1. Any previous JAK2 inhibitor treatment prior to study enrolment, with the exception of Ruxolitinib
    2. Hypersensitivity to JAK inhibitor
    3. Clinical or laboratory evidence of cirrhosis
    4. Prior allogeneic transplant for any hematopoietic disorder
    5. Greater than 20% blast in the PB (peripheral blood)or BM (bone marrow) prior to HCT or had leukemic transformation (greater than 20% blasts in PB or BM any time prior to HCT)
    6. Syngeneic donor
    7. Cord Blood transplant
    8. Active uncontrolled infection
    9. History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET
    10. Known Human Immunodeficiency Virus (HIV) positive
    11. Pregnancy at the time of transplant
    12. Any other concurrent illness which in Investigator’s opinion puts the patient at excessive risk of treatment related toxicities
    13. Unable to give informed consent
    14. Active infection with hepatitis A,B or C virus
    15. Subjects who require therapy with a strong CYP3A4 (Cytochrome P450 3A4) inhibitor prior to enrolment to this study
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective of this study is to estimate the proportion of patients who experience graft failure or death by day 100 post transplant, in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.
    E.5.1.1Timepoint(s) of evaluation of this end point
    100 days post-transplant
    E.5.2Secondary end point(s)
    1. Neutrophil and platelet recovery
    2. Non-relapse mortality (NRM) at 100 days and 1-year
    3. Acute and chronic GvHD at 1-year
    4. Chimerism studies at 30, 60 and 100 days post transplant
    5. Remission status according to IWG-MRT criteria (1) at day 100, and 6 and 12 months post transplant
    6. Relapse/progression (defined as per IWG-MRT criteria) (1) at 1-year post transplant
    7. Progression-free survival at 1-year
    8. Overall Survival at 1-year
    9. Impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life
    10. Expression profiling and measurements of cytokines prior to start of Ruxolitinib, prior to start of chemotherapy for conditioning, day +30 and day +100 post transplant
    11. Association of cytokines levels with acute and chronic GvHD
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 30, Day 60 Day 100 post-transplant
    One year post-transplant
    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 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 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) 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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Israel
    United States
    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 years3
    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 years4
    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: 63
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 23
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 25
    F.4.2.2In the whole clinical trial 86
    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)
    Once the research phase of the study has been completed, patients will be followed-up according to standard clinical care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Myeloproliferative Disorders Research Consortium
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-06-14
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