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    The EU Clinical Trials Register currently displays   34900   clinical trials with a EudraCT protocol, of which   5686   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2004-004685-32
    Sponsor's Protocol Code Number:P02978
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2006-05-12
    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 ConcernedGermany - BfArM
    A.2EudraCT number2004-004685-32
    A.3Full title of the trial
    A Pivotal Randomized Study of Lonafarnib (SCH66336) Versus Placebo in the Treatment of Subjects With Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) Who Are Platelet Transfusion Dependent With or Without Anemia
    A.3.2Name or abbreviated title of the trial where available
    A pivotal study in CMML/MDS
    A.4.1Sponsor's protocol code numberP02978
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSchering-Plough Research Institute
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameLonafarnib
    D.3.2Product code SCH 66336
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLonafarnib
    D.3.9.1CAS number 193275-84-2
    D.3.9.2Current sponsor codeSCH 66336
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.IMP: 2
    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 nameLonafarnib
    D.3.2Product code SCH 66336
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLonafarnib
    D.3.9.1CAS number 193275-84-2
    D.3.9.2Current sponsor codeSCH 66336
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    D.8.3Pharmaceutical form of the placeboCapsule*
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Platelet Transfusion Dependence in Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) according to FAB criteria
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the clinical benefit of lonafarnib compared to placebo, where benefit is measured by proportion of subjects that achieved platelet transfusion independence for any 8-consecutive-week period after randomization without worsening of red blood cell (RBC) transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period of platelet transfusion independence.
    E.2.2Secondary objectives of the trial
    To compare the hematologic response rate (complete remission, partical remission, hematologic improvement), 4-weekly RBC transfusion events (number of RBC transfusion events during a 4-week period), active bleeding events (number and severity), infections (number of CTCAE Grade 3 and 4 infections and days of acute antibiotic, antifungal and/or antiviral intervention), and safety between the two groups. Additionally subjects will be followed for survival (In Germany for an maximum of 5 years per patient). Pharmacokinetics, pharmacodynamics and pharmacogenomics will be assessed at participating sites in subjects who consented to participate. (This substudy will not be performed in Germany).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subject has pathologically documented MDS according to FAB classification confirmed by bone marrow aspirate (BMA) conducted prior to randomization
    To be eligible for prospective screening: Subject has platelet and RBC transfusion data, and hemoglobin and platelet values available for the immediately preceding 8-week period (i.e., the retrospective screening period) prior to study enrollment. In addition, the following requirements must be satisfied.
    Subjects must have received 1 to 8 platelet transfusion events during the first 4-week interval (Day -84 to Day -57) and 1 to 8 platelet transfusion events during the second 4-week interval (Day -56 to Day -29) of the 8-week retrospective screening period.
    The number of platelet transfusion events during the first 4 weeks of the retrospective screening period (Day -84 to Day -57) and the second 4 weeks of the retrospective screening period (Day -56 to Day -29) must not differ by greater than 4.
    If the subject is RBC transfusion-dependent, the number of RBC transfusion events during the first 4 weeks of the retrospective screening period (Day -84 to Day -57) and the second 4 weeks of the retrospective screening period (Day -56 to Day -29) must not differ by greater than 4.
    To be eligible for randomization: The platelet and RBC transfusion values obtained during the 4-week prospective screening (Day -28 to Day -1) should confirm the results of the retrospective screening phase. In addition, subject must meet the following other requirements in order to be randomized.
    Subject must have received 1 to 8 platelet transfusion events during each of the three 4-week periods (Day -84 to -57, Day -56 to Day -29, Day -28 to Day -1) prior to randomization.
    The number of platelet transfusion events during each of the three 4-week periods prior to randomization must be within +/- 2 of the average number of the transfusion events per 4-week period during the entire 12-week period (Day -84 to Day -1) prior to randomization.
    For RBC transfusion independent subjects, the average hemoglobin value during the first 4- weeks and second 4-weeks retrospective screening period, must not differ by greater than 2g/dL from the average hemoglobin value obtained during the prospective screening period (day -28 to Day -1).
    For RBC transfusion dependent subjects, the number of RBC transfusion events during each of the three 4-week periods must be within +/- 2 of the average number of RBC transfusion events during the entire 12 –week period prior to randomization.
    There should be no change in the reasons for transfusions given during the retrospective versus the prospective screening period (i.e. fixed transfusion criteria selected on Day -28 should apply for all transfusions given during the prospective screening period).
    Subject is ≥18 years old at the start of the study drug administration
    Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 on Day -1
    Subject is either refractory to, not eligible for, or unwillingly to undergo other existing standard tumor treatments.
    Greater than 12 weeks (from randomization on Day-1) from any treatment with Oprelvekin, and treatment with erythropoetin or darbopoetin, unless given in stable doses over the 12 week screening period.

















    E.4Principal exclusion criteria
    Subject has chemotherapy- or radiotherapy-associated MDS (i.e., secondary MDS)
    Subject has a history of AML (> 30% bone marrow blasts)
    Subject has received a bone marrow or peripheral blood stem cell transplant or has received a donor lymphocyte infusion.
    Subject has a known history of immune thrombocytopenic purpura (ITP).
    Subject has received chemotherapy, radiotherapy, immunotherapy, or other MDS-directed therapy (except best supportive care) within 12 weeks prior to randomization.
    Subject has Grade ≥2 nausea or Grade ≥1 vomiting (despite adequate antiemetic medication) or any condition that could interfere with administration of an oral medication
    Subject has a marked baseline prolongation of the QTc interval, CTCAE Grade ≥1
    Subject has known HIV or AIDS- related illness
    Subject has previously received a farnesyl transferase inhibitor
    Subject has been administered ketoconazole within 72 hours prior to study drug administration.
    No serum creatinine > 1.5 x upper limit of normal (ULN).
    No bilirubin > 2mg/dl with the exception of documented Gilbert's Syndrome.
    No AST/SGOT or ALT/SGPT > 2.5 x ULN, or Alkaline phosphatase > 4 x ULN.

    E.5 End points
    E.5.1Primary end point(s)
    The achievement of platelet transfusion independence for any 8-consecutive-week period with no worsening of RBC transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period.
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Open-label option for non-responders on placebo at end of Cycle 3
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    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 concerned5
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial 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
    Non response (not achieving platelet transfusion independence for at least 4-consecutive weeks- with no worsening of RBC or HG value.

    Transformation to Acute Myelogenous Leukemia (AML) for RA, RARS, RAEB, CMML
    Disease progression (increase of blast counts of ≥50%) for RAEB-T
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 200
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2005-11-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-11-17
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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