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   43861   clinical trials with a EudraCT protocol, of which   7284   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:2017-002194-18
    Sponsor's Protocol Code Number:CA209-9P9
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-01-10
    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 ConcernedGermany - PEI
    A.2EudraCT number2017-002194-18
    A.3Full title of the trial
    Phase 1/2 Trial to determine the Response Rate of Nivolumab in Acute Myeloid Leukemia (AML) relapse after Allogeneic Hematopoietic Cell Transplantation (allo-HCT)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 1/2 trial to test Nivolumab in treatment failure of Acute Myeloid Leukemia (AML) after stem cell transplantation by a allogenic donor (allo-SCT)
    A.4.1Sponsor's protocol code numberCA209-9P9
    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 SponsorMedical Center - University of Freiburg
    B.1.3.4CountryGermany
    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 supportUniversity of Freiburg, Faculty of Medicine
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportBristol-Myers Squibb
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversitätklinikum Freiburg, Klinik für Innere Medizin 1
    B.5.2Functional name of contact pointEarly Clinical Trial Unit
    B.5.3 Address:
    B.5.3.1Street AddressHugstetter Str. 55
    B.5.3.2Town/ cityFreiburg
    B.5.3.3Post code79106
    B.5.3.4CountryGermany
    B.5.4Telephone number+49761270-36710
    B.5.5Fax number+49761270-33180
    B.5.6E-mailstuz.NIFAR@uniklinik-freiburg.de
    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.3.4Pharmaceutical 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.3.9.3Other descriptive nameNIVOLUMAB
    D.3.9.4EV Substance CodeSUB122750
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acute myeloid leukemia relapse after allo-HCT
    E.1.1.1Medical condition in easily understood language
    Acute myeloid leukemia relapse
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10001941
    E.1.2Term AML
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10066572
    E.1.2Term AML progression
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Overall response rate (ORR) to treatment after 6 and 12 weeks of induction therapy
    E.2.2Secondary objectives of the trial
    To assess time to treatment response
    To assess rate of patients with treatment failure
    To assess duration of response
    To assess Overall Survival (OS)
    To assess Progression-free surviv-al (PFS)
    To assess Non Relapse Mortality (NRM)
    To assess changes in alloreactive T cell phenotype and metabolism during treatment
    To assess quality of life
    To assess incidence and severity of GvHD
    To assess incidence of infectious complications
    To assess the incidence and severity of immune-related adverse events
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Relapse of AML after allo-HCT from any donor source (matched unrelated donor, mismatched unrelated donor, sibling, haploidentical) using bone marrow or peripheral blood stem cells at 3 months or more after allogeneic HCT. Patients can be rescreened.
    2. Cytological or histological evidence of AML relapse including but not limited to bone marrow biopsy, extramedullary site biopsy or cerebrospinal fluid evaluation.
    3. No immune suppression for at least 2 weeks prior to screening
    4. 10% or more donor-derived chimerism measured within 4 weeks prior to day 0
    5. Male and female patients aged ≥18 years
    6. ECOG performance status 0, 1, or 2
    7. No other superior treatment approach (second allo-HCT) available
    8. At least 1 cycle of therapy with the hypomethylating agents decitabine or azacitidine between diagnosis of relapse and screening
    9. Written informed consent
    10. Ability to understand the nature, significance and consequences of the study and the study-related procedures and to comply with them.
    E.4Principal exclusion criteria
    1. History or active acute GvHD grade III/IV
    2. Chronic GvHD requiring systemic immunosuppressive treatment at the time of screening
    3. Active autoimmune diseases
    4. Active treatment in a clinical study of any investigational agent within 30 days prior day 0 or within 5 half-lives of the study treatment, whichever is greater
    5. Mechanical ventilation or patients who have resting O2 saturation <90% by pulse-oximetry, require vasopressors, and/or have NYHA class III or IV heart failure
    6. Abnormal liver function tests (serum total bilirubin 1,5 x ULN; or in case of liver infiltration by AML, serum (total) bilirubin > 5 x ULN, serum alanine or aspartate aminotransferase >3 × ULN or in case of liver infiltration by AML, AST and/or ALT > 5 x ULN)
    7. Abnormal kidney function tests (calculated creatinine clearance ≤30 ml/min by the Cockcroft-Gault equation)
    8. Severe hematological impairment (platelets <10 000/µl, hemoglobin level <8 mg/dl unless attributable to AML infiltration of the BM), there is no lower limit for neutrophil counts because AML relapse leads to low neutrophil numbers and treatment with nivolumab could improve this by eradicating the leukemia
    9. Active uncontrolled bacterial, viral or fungal infection
    10. Positivity for HIV, Hepatitis B or Hepatitis C at the time of screening
    11. Active or latent tuberculosis infection that has developed after allo-HCT
    12. Previous or concurrent malignancies within the last 3 years of enrolment except for adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for more than 3 years
    13. Uncontrolled hypertension or ventricular arrhythmias
    14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
    15. Known allergies, hypersensitivity, or intolerance of the study medication, excipients, or similar compounds
    16. Female patients who are pregnant or breast feeding
    17. Female patients of child-bearing potential who are not willing to use highly effective methods of contraception during the trial and at least 5 months after the last dose of nivolumab (see also 10.9)
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR) at weeks 6 and 12 after treatment start.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Weeks 6 and 12 after treatment start
    E.5.2Secondary end point(s)
    Time to response is defined as time from treatment start to the date of first documentation PR, CR, CRi or morphologic leukemia-free state. Death without prior response will be considered to be a competing event.
    Rate of patients with treatment failure until month 3 after treatment start.
    The duration of response is assessed for responders only by calculating the time from first response to the date of first observation of AML relapse/progression or the date of additional systemic treatment for AML. Death without prior observation of disease progres-sion is considered as a competing event.
    OS is defined as time from treatment start to the date of death from any cause.
    PFS is defined as the time from treatment start to the date of recurrence or progression of AML or death from any cause, whichever occurs first
    NRM is defined as the time from treatment start to the date of death not preceded by hematologic dis-ease recurrence.
    Hematologic disease recurrence / progression is considered to be a competing event
    Changes in alloreactive T cell phenotype and metabolism
    EORTC QLQ-C30 and EORTC QLQ-C29
    Cumulative incidence rates of patients who develop acute or chronic GvHD as defined by the diagnostic criteria of the Harris et al for acute GvHD20 and according to the NIH criteria for chronic GvHD21. Death without prior GvHD is considered as a competing event
    Rate of patients who develop bacterial, viral or fun-gal infections which require pharmacological treat-ment (cumulative incidence rate)
    Frequency and severity of immune-mediated adverse events
    E.5.2.1Timepoint(s) of evaluation of this end point
    18 months after randomization of last patient
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    New therapeutic indication (AML after Allo-SCT)
    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 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 concerned2
    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 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months33
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    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 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 state20
    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)
    After the end of study, control examinations take place according to the present standard of care of the participating clinic.
    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 Decision2018-03-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-11-24
    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-Thu Apr 25 21:55:07 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA