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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41046   clinical trials with a EudraCT protocol, of which   6718   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) .
     
    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:2018-002115-96
    Sponsor's Protocol Code Number:SCC215/P002900
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-18
    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 - BfArM
    A.2EudraCT number2018-002115-96
    A.3Full title of the trial
    Optimizing MATRix as remission induction in PCNSL:
    De-escalated induction treatment in newly diagnosed primary CNS lymphoma
    – a randomized phase III trial
    Optimierung der Induktionstherapie mit MATRix (Methotrexat, Ara-C, Thiotepa, Rituximab) durch De-Eskalation bei primären ZNS-Lymphomen - eine randomisierte Phase III Studie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Optimizing MATRix, a combination of Methotrexate, Ara-C, Thiotepa and Rituximab given as an induction therapy, de-escalated in duration and total drug dose in comparison to the standard induction therapy and both treatments followed by a high dose therapy with autologous stem cell transplantation. The therapy is for patients with newly diagnosed primary lymphoma of the central nervous system.
    Optimierung einer in Dauer und Gesamtdosis abgeschwächten, einleitenden Therapie mit MATRix, einer Medikamentenkombination, bestehend aus Methotrexat, ARA-C, Thiotepa und Rituximab im Vergleich zur Standard Einleitungstherapie; beiden folgt eine Hochdosistherapie und autologe Stammzelltransplantation. Die Behandlung ist für Patienten mit neu diagnostizierten primären Lymphomen des zentralen Nervensystems.
    A.3.2Name or abbreviated title of the trial where available
    OptiMATe
    OptiMATe
    A.4.1Sponsor's protocol code numberSCC215/P002900
    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 SponsorKlinikum Stuttgart, Landeshauptstadt Stuttgart gKAöR
    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 supportBMBF Federal Ministry of Education and Research
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClinical Trials Unit, Medical Center -University of Freiburg
    B.5.2Functional name of contact pointElvira Burger, Project Management
    B.5.3 Address:
    B.5.3.1Street AddressElsaesser Strasse 2
    B.5.3.2Town/ cityFreiburg
    B.5.3.3Post code79110
    B.5.3.4CountryGermany
    B.5.4Telephone number004976127073780
    B.5.5Fax number004976127024225
    B.5.6E-mailelvira.burger@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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRituximab
    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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    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) Yes
    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.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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameMethotrexate
    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 INNMETHOTREXATE DISODIUM
    D.3.9.1CAS number 7413-34-5
    D.3.9.3Other descriptive nameMTX, IUPAC: (2S)-2-[[4-[(2, 4-diaminopteridin-6-yl)methylmethylamino] benzoyl]amino]pentanedioate disodium
    D.3.9.4EV Substance CodeSUB16442MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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) 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.IMP: 3
    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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCytarabine
    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 INNCYTARABINE
    D.3.9.1CAS number 147-94-4
    D.3.9.3Other descriptive nameCytosine Arabinoside, Arabinofuranosylcytosin, Ara-C, IUPAC: 4-amino-1- [(2R,3S,4R,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-on
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.IMP: 4
    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.2.5The 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 nameThiotepa
    D.3.4Pharmaceutical form Powder for 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 INNTHIOTEPA
    D.3.9.1CAS number 52-24-4
    D.3.9.3Other descriptive nameIUPAC: 1,1 ',1"-phosphorothioyltriaziridine
    D.3.9.4EV Substance CodeSUB10985MIG
    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 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.IMP: 5
    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.2.5The 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 nameCarmustine
    D.3.4Pharmaceutical form Powder and solvent 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 INNCARMUSTINE
    D.3.9.1CAS number 154-93-8
    D.3.9.3Other descriptive nameBCNU, Bischlorethylnitrosourea, IUPAC: 1,3-Bis(2-chloroethyl)-1-nitrosourea
    D.3.9.4EV Substance CodeSUB06132MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3.3
    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.IMP: 6
    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.2.5The 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 nameBusulfan
    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 INNBUSULFAN
    D.3.9.1CAS number 55-98-1
    D.3.9.3Other descriptive nameBU, IUPAC: Butane-1,4-diyl dimethanesulfonate
    D.3.9.4EV Substance CodeSUB05993MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3.2
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system is a rare disorder confined to the cerebral parenchyma, leptomeninges, eyes or spinal cord. It accounts for 4 to 6% of all Non-Hodgkin’s lymphomas and for 3 to 4% of all primary brain tumors. Incidence of PCNSL has increased over the past 30 years, particularly in immunocompetent individuals.
    With a median survival of 3 months in untreated individuals, prognosis of PCNSL resembles that of systemic high-grade NHL.
    Primäres diffuses großes B-Zell-Lymphom (DLBCL) des zentralen Nervensystems ist eine seltene Erkrankung der zerebalen Parenchyma, Leptomeninges, der Augen oder des Rückenmarks. Sie macht 4-6% aller Non-Hodgkin Lymphome (NHL) und 3-4% aller primären Hirntumore aus. Die Inzidenz von PZNSL ist in den vergangenen 30 Jahren angestiegen vor allem bei immunkompeten Patienten. Die durchschnittliche Überlebensrate bei unbehandelten Patienten liegt bei 3 Monaten.
    E.1.1.1Medical condition in easily understood language
    Primary diffuse large B-cell lymphoma of central nervous system, a rare disorder confined to the brain and spinal cord. The disease may be fatal within a short period of time when remained untreated.
    ZNSNHL ist eine seltene Erkrankung des lymphat. Systems im Bereich Gehirn/Rückenmark. Es handelt sich dabei um bösartiger Immunzellen. Die Krankheit kann unbehandelt in kurzer Zeit zum Tode führen.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary: To demonstrate superiority of a de-escalated induction treatment strategy followed by autologous stem cell transplantation compared to the standard MATRix protocol in terms of event free survival (EFS)
    Primäres Ziel: Nachweis der Überlegenheit der deeskalierten Induktion gefolgt von einer autologen Stammzelltransplantation im Vergleich zum Behandlungsstandard MATRix hinsichtlich des Endpunktes ereignisfreies Überleben.
    E.2.2Secondary objectives of the trial
    Secondary: To compare overall survival, progression free survival, remission rate prior to consolidation and after consolidation, complication rate, neurocognitive impairment and quality of life between both treatment arms
    Sekundäres Ziel: Der Vergleich zwischen den beiden Behandlungsarmen hinsichtlich des Gesamtüberlebens, des progressionsfreies Überlebens, der Remissionsrate vor und nach der Konsolidierungstherapie, der Komplikationsrate, neurokognitiver Beeinträchtigungen und der Lebensqualität.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system.
    2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
    3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
    4. Disease exclusively located in the CNS.
    5. At least one measurable lesion.
    6. Previously untreated patients (previous or ongoing steroid treatment admitted).
    7. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
    8. Ability to understand the nature of the trial and the trial related procedures and to comply with them.
    9. Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation.
    1. Immunkompetente Patienten und Patientinnen mit Erstdiagnose eines primären B-Zell- Lymphoms (DLBCL) des zentralen Nervensystems
    2. Patienten und Patientinnen Alter 18-65 Jahre unabhängig vom ECOG oder 66-70 Jahre mit ECOG Performance Status ≤ 2
    3. Histologisch oder zytologisch gesicherte Diagnose eines primären B-Zell-Lymphoms des zentralen Nervensystems durch den lokalen Pathologen. Diagnosensicherung mittels stereotaktischer oder offener Biopsie, Liquorzytologie oder Vitrektomie
    4. Krankheit ausschließlich lokalisiert in ZNS, Liquor oder den Hirnnerven.
    5. Mindestens eine messbare Läsion
    6. Patienten ohne Vorbehandlung (eine bereits erfolgte oder noch andauernde Behandlung mit Steroiden ist erlaubt)
    7. Unterzeichnung der Einwilligungserklärung entsprechend den internationalen Richtlinien und der nationalen Gesetzgebung durch den Patienten oder einen autorisierten gesetzlichen Vertreter – für den Fall, dass der Patient krankheitsbedingt nicht in der Lage dazu ist.
    8. Die Fähigkeit, die Art der Studie und deren Inhalte zu verstehen
    9. Sexuell aktive Patienten und Patientinnen im fortpflanzungs-fähigen Alter, die zugestimmt haben, während Ihrer gesamten Studienteilnahme adäquat zu verhüten
    E.4Principal exclusion criteria
    1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
    2. Systemic lymphoma manifestation (outside the CNS).
    3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
    4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
    5. Previous Non-Hodgkin lymphoma at any time.
    6. Inadequate renal function (clearance < 60 ml/min).
    7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
    8. Active hepatitis B or C disease.
    9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
    10. Third space fluid accumulation > 500 ml.
    11. Hypersensitivity to study treatment or any component of the formulation.
    12. Taking any medications that are likely to cause interactions with the study medication
    13. Known or persistent abuse of medication, drugs or alcohol.
    14. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
    15. Previous participation in this trial.
    16. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
    17. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
    18. Current or planned pregnancy, nursing period
    19. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device; hormonal contraception in combination with a mechanical method of contraception
    1. Kongenitale oder erworbene Immunschwäche einschließlich HIV-Infektion und Organtranplantationen in der Vergangenheit.
    2. Systemische Lymphom-Manifestation (außerhalb des ZNS)
    3. Isoliertes okuläres Lymphom ohne Manifestation im Hirnparenchym oder im Rückenmark
    4. Andere bösartige Erkrankungen; ausgenommen sind chirurgisch entfernte Karzinome in situ der Zervix, Karzinome der Haut und andere bösartige Tumoren, die sich seit mindestens 5 Jahren in kompletter Remission befinden.
    5. Diagnostiziertes Non-Hodgkin Lymphom in der Vergangenheit
    6. Inadäquate renale Funktion (Kreatinin-Clearance < 60 ml/min).
    7. Inadequates Knochenmark, inadäquate kardiale Leistung, inadäquate Leber- oder Lungenfunktion gemäß Einschätzung Prüfer/Prüferin
    8. Active hepatitis B or C Erkrankung.
    9. Laufende Behandlung mit anderen Studienmedikamenten oder Teilnahme an einer klinischen Studie innerhalb der letzten 30 Tage vor Beginn dieser Studie.
    10. Flüssigkeitsansammlung im 3. Raum > 500 ml.
    11. Überempfindlichkeit gegenüber der Studienmedikation oder einen anderen Bestandteil der Behandlung.
    12. Einnahme von Medikamenten, die mit großer Wahrscheinlichkeit zu Wechselwirkungen mit der Studienmedikation führen
    13. Bekannter oder anhaltender Missbrauch von Arzneimitteln, Drogen oder Alkohol
    14. Nicht geschäftsfähiger Patient ,der Art, Bedeutung und Konsequenzen der Studie nicht erfassen und verstehen kann und keinen gesetzlichen Betreuer hat.
    15. Teilnahme an der Vorgängerstudie Matrix
    16. Personen, die sich in einem Abhängigkeitsverhältnis zum Sponsor und/oder Prüfarzt/Prüfärztin befinden
    17. Jeglicher familiärer, soziologischer oder geographischer Umstand, der potentiell die ordnungsgemäße protokollgerechte Durchführung der Studie und der Nachbeobachtung gefährdet
    18. Bestehende oder geplante Schwangerschaft, Stillzeit
    19. Geschlechtsreife Patienten, die sich weigern, für die Dauer der Studienteilnahme Verhütungsmittel zu verwenden: Intrauterinpassar; Hormonverhütung in Verbindung mit einer mechanischen Verhütungsmethode
    E.5 End points
    E.5.1Primary end point(s)
    Primary End Points:
    Event-free survival
    Primärer Endpunkt:
    Ereignisfreies überleben
    E.5.1.1Timepoint(s) of evaluation of this end point
    Defined as time from randomization to premature end of treatment due to any reason, new anti-lymphoma treatment, lymphoma progression or death, whichever occurs first
    Definiert als Zeit ab Randomisierung bis zum vorzeitigen Ende der Behandlung egal aus welchem Grund; im Fall von neuen Behandlungsmethoden der Lymphomerkrankung, bei Progression oder Tod, je nachdem, was zuerst eintritt.
    E.5.2Secondary end point(s)
    - Overall survival (OS)
    - Progression free survival (PFS)
    - Remission prior to consolidation therapy – RA II
    - Remission after consolidation – 30 days after autologous stemcell transplantation (ASCT)
    - Rate of patients reaching consolidation
    - Quality of life (QOL): EORTC QLQ-C30, EORTC QLQ-BN20; measured during screening period, at response assessment II after completion of induction treatment, 30 days after ASCT and thereafter every 12 months during follow-up.
    - Gesamtüberleben:
    - Progressionsfreies Überleben
    - Remission vor der Konsolidierungstherapie–Response Assessment II
    - Remission nach der Konsolidierung
    - Anteil Patienten, welche die Konsolidierungstherapie erreichen
    - Lebensqualität (QLQ): EORTC QLQ30, EORTC QLQ-BN20
    E.5.2.1Timepoint(s) of evaluation of this end point
    - OS: is defined as time from randomization until death from any cause
    - PFS: is defined as time from randomization until disease progression, relapse or death from any cause
    - Remission prior to consolidation: determined at RA II and divided in CR, uCR, PR, SD, PD according to IPCG criteria
    - Remission after consolidation: 30 days after autologous stemcell transplantation (ASCT)
    - Rate of patients reaching consolidation: is defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm)
    - QLQ: performed at screening, RA II and with beginning of RA III every 12 months until end of follow-up
    - Gesamtüberleben: definiert als Zeit ab Randomisation bis zum Tod egal aufgrund welcher Ursache
    - Progressionsfreies Überleben: definiert als Zeit ab Randomisierung bis zur Krankheitsprogression, Wiedererkrankung, oder Tod egal aufgrund welcher Ursache
    - Remission vor Konsolidierung: zum Response Assesment II, aufgeteilt in CR, uCR, PR, SD, PD gemäß IPCG Kriterien
    - Remission nach der Konsolidierung: 30 Tage nach der autologen Stammzelltransplantation (ASZT)
    - Anteil Patienten, welche die Konsolidierungstherapie erreichen: nach Erhalt mindestens der ersten Dosis der Konsolidierungstherapie, gefolgt von 1 Zyklus R/HD-MTX und 2 Zyklen Matrix im experimentellen Arm
    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) 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 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 Yes
    E.8.2.3.1Comparator description
    Vergleich Induktiontherapy Arm A Kontrollarm / Arm B experimentelle Behandlung
    Comparison Induction Treatment Arm A control treatment / Arm B experimental treament
    E.8.2.4Number of treatment arms in the trial2
    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 concerned35
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    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
    Austria
    Switzerland
    United Kingdom
    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
    LPLV
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years9
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years9
    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: 249
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 77
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients, who are temporarily legally not competent due to their disease,which is not unusual, may be inlcuded if he/she has an authorized legal representative. Usually the patients regain their competence after having startet the treatment.
    .
    Patienten, die krankheitsbedingt, was nicht ungewöhnlich ist bei dieser Erkrankung, zeitweilig nicht in der Lage sind, aufgeklärt zu werden, die aber einen autorisierten gesetzlichen Vertreter haben, können an der Studie teilnahmen.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state326
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 326
    F.4.2.2In the whole clinical trial 326
    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)
    Further annual control examinations are recommended, after the patient has finished the study treatment and the follow up period.
    Es wird empfohlen, dass der Patient auch nach der Studienteilnahme inkl. Nachbeobachtungszeit weiterhin zu jährlichen Kontrolluntersuchungen kommen soll.
    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 Decision2021-04-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-22
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA