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    Summary
    EudraCT Number:2017-003150-16
    Sponsor's Protocol Code Number:COUP-1
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-07-31
    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 ConcernedAustria - BASG
    A.2EudraCT number2017-003150-16
    A.3Full title of the trial
    Copanlisib and Rituximab in Marginal Zone Lymphoma Patients
    Copanlisib and Rituximab bei Patiente mit Marginalzonenlymphom
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Copanlisib and Rituximab in Marginal Zone Lymphoma Patients
    Copanlisib and Rituximab bei Patiente mit Marginalzonenlymphom
    A.3.2Name or abbreviated title of the trial where available
    COUP-1
    A.4.1Sponsor's protocol code numberCOUP-1
    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 Hospital Ulm
    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 supportBayer Healthcare AG
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportCelltrion Healthcare Co., Ltd
    B.4.2CountryKorea, Republic of
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospital Ulm
    B.5.2Functional name of contact pointProf. Dr. med. Christian Buske
    B.5.3 Address:
    B.5.3.1Street AddressAlbert-Einstein-Allee 23
    B.5.3.2Town/ cityUlm
    B.5.3.3Post code89081
    B.5.3.4CountryGermany
    B.5.4Telephone number+49 73150065800
    B.5.5Fax number+4973150065802
    B.5.6E-mailChristian.Buske@uni-ulm.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 Aliqopa
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER Healthcare Pharmaceuticals Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameCopanlisib
    D.3.2Product code BAY84-1236
    D.3.4Pharmaceutical form Lyophilisate 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 INNCOPANLISIB
    D.3.9.1CAS number 1032568-63-0
    D.3.9.2Current sponsor codeBAY 84-1236
    D.3.9.3Other descriptive nameBAY 80-6946 (AS DIHYDROCHLORID BAY 84-1236)
    D.3.9.4EV Substance CodeSUB184952
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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: 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.2.1.1.1Trade name Truxima
    D.2.1.1.2Name of the Marketing Authorisation holderCelltrion Healthcare Hungary Kft.
    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 nameTruxima
    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.3.9.3Other descriptive nameTruxima
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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.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.2.1.1.1Trade name Truxima
    D.2.1.1.2Name of the Marketing Authorisation holderCelltrion Healthcare Hungary Kft.
    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 nameTruxima
    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.3.9.3Other descriptive nameTruxima
    D.3.9.4EV Substance CodeSUB12570MIG
    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 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
    Marginal Zone Lymphoma
    Marginalzonen Lymphome
    E.1.1.1Medical condition in easily understood language
    Marginal Zone Lymphoma
    Marginalzonen Lymphome
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10062113
    E.1.2Term Splenic marginal zone lymphoma
    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 10076596
    E.1.2Term Marginal zone lymphoma
    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
    The objective of the trial is to test the efficacy and toxicity of the treatment of Copanlisib/Rituximab in patients with MZL in need of treatment, who have failed or are not eligible for local therapy or relapsed after local or systemic therapy. For efficacy the rate of complete remissions (according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for non-gastric extranodal, nodal and splenic MZL) after induction therapy will be primarily analysed [4-7]. For toxicity treatment associated adverse events, quality of life and cumulative incidence of secondary malignancies will be documented.
    Ziel der Studie ist es, die Wirksamkeit und Toxizität der Therapie mit Copanlisib/Rituximab bei Patienten mit behandlungsbedürftigem MZoL, die auf lokale Therapiemodalitäten oder eine systemische Therapie entweder nicht angesprochen haben oder für eine lokale Therapie nicht in Frage kommen, zu testen. Zum Wirksamkeitsnachweis wird primär die Rate vollständiger Remissionen (nach den GELA-Kriterien für Magen-MALT oder nach Cheson 2007 Kriterien für nicht-gastrische extranodale, nodale und splenische MZoL) nach Induktionstherapie analysiert [6-9]. Zur Toxizitätsbeurteilung werden das Auftreten behandlungsassoziierter unerwünschte Ereignisse, die Lebensqualität und die kumulative Inzidenz von sekundären Malignomen dokumentiert.
    E.2.2Secondary objectives of the trial
    • Response rate (CR, PR, CR or PR)
    • Best response
    • Time to best response
    • Time to first response
    • Progression free survival (PFS)
    • Time to treatment failure (TTF)
    • Duration of Response (DR)
    • Cause specific survival (CSS)
    • Overall survival (OS)
    • Quality of life during induction and maintenance therapy
    • Gesamtansprechraten (CR, PR, CR oder PR)
    • Bestes Therapieansprechen
    • Zeit bis zum besten Therapieansprechen
    • Zeit bis zum ersten Therapieansprechen
    • Progressionsfreies Überleben
    • Zeit bis zum Behandlungsversagen
    • Remissionsdauer
    • Ursachenspezifisches Überleben
    • Gesamtüberleben
    • Lebensqualität während der Induktions- und Erhaltungstherapie
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must have a proven pathological diagnosis of MZL, diagnosed by a reference pathology center.
    Patients must meet the following inclusion criteria to be eligible for participation in this study:
    – Confirmed CD20 positive de novo or relapsed MALT Lymphoma in need of treatment following or being not eligible for local therapy (including surgery, radiotherapy and antibiotics e.g. for H. pylori-positive gastric lymphoma arisen at any extranodal site)
    OR
    – Confirmed CD20 positive de novo or relapsed splenic MZL in need of treatment following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus)
    OR
    – Confirmed CD20 positive de novo or relapsed nodal MZL in need of treatment following or not being eligible for local therapy (radiotherapy)
    For nodal MZL and extragastric MALT lymphoma:
    – At least one bi-dimensionally measurable lesion (≥ 1.5 cm in its largest dimension by CT scan or MRI). Please refer to Appendix C.
    For SMZL:
    For splenic MZL, an enlarged spleen on CT scan and lymphoma cell infiltration has to be seen in bone marrow and/or peripheral blood. Please refer to Appendix E.
    At least one of the following criteria must be met:
    – Bulky progressive or painful splenomegaly
    – one of the following symptomatic/progressive cytopenias : Hb < 10 g/dL, or Plat < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration)
    – SMZL with concomitant hepatitis C infection which has not responded to or has relapsed after Interferon and/or Ribavirin and/or direct antiviral agents (patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA).
    – splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites if not being eligible for local therapy.

    For gastric MALT Lymphoma:
    For gastric MALT lymphoma, the clinical evidence of the MZL as seen by gastroendoscopy is sufficient. There is no need to show a measurable lesion by CT scan or MRI. Please refer to Appendix D.
    Inclusion is possible for patients with:
    – H. pylori-negative disease de novo or following or being not eligible for local therapy (i.e., surgery, radiotherapy or antibiotics) or after systemic therapy.
    - H. pylori-positive disease that has remained stable, progressed, or relapsed following antibiotic therapy.
    Patienten müssen eine nachgewiesene pathologische Diagnose eines MZoL haben, diagnostiziert durch ein Referenzpathologiezentrum.
    Patienten müssen folgenden Einschlusskriterien erfüllen, um an dieser Studie teilnehmen zu können
    – bestätigtes CD20-positives de novo oder rezidiviertes MALT-Lymphom jeden extranodalen Ursprungs, ineligibel oder nach einer Lokaltherapie (einschließlich Operation, Radiotherapie und Antibiotika, z.B. für H. pylori-positives Magenlymphom) mit Behandlungsindikation
    ODER
    – bestätigtes CD20-positives de novo oder rezidiviertes splenisches MZol ineligibel oder nach einer Lokaltherapie (einschließlich Operation oder einer antiviralen Hepatitis C Therapie) mit Behandlungsindikation
    ODER
    – bestätigtes CD20-positives de novo oder rezidiviertes nodales MZol ineligibel oder nach einer Lokaltherapie (Radiotherapie) mit Behandlungsindikation
    Für nodale Marginalzonenlymphome und extragastrische MALT-Lymphome:
    – zumindest eine zweidimensional messbare Läsion (≥ 1.5 cm in der längsten Dimension durch CT oder MRT). Siehe auch Appendix C.
    Für splenische Marginalzonenlymphome:
    Für splenische MZL muss eine vergrößerte Milz im CT und Lymphomzelleninfiltration im Knochenmark und/oder peripheren Blut vorliegen. Siehe auch Appendix E.
    Mindestens eins der folgenden Kriterien muss erfüllt sein:
    – progrediente bulkartige oder schmerzhafte Splenomegalie
    - einer der folgenden symptomatischen/progredienten Zytopenien: Hb < 10 g/dL, oder Thrombozyten < 80.000 /µL, oder Neutropenie < 1000 /µL, unabhängig von der Ursache (autoimmune bedingt oder Hypersplenismus oder Knochenmarkinfiltration)
    – splenische Marginalzonenlymphome mit Hepatitis C-Infektion, die auf Interferon und / oder Ribavirin nicht angesprochen haben oder nach Interferon und / oder Ribavirin und / oder direkt antiviralen Mitteln rezidiviert sind (Patienten mit positivem HCV-Antikörper-Test sind nur teilnahmeberechtigt bei negativem PCR-Test für HCV RNA)
    – splenektomierte Patienten mit rasch ansteigender Lymphozytenzahl, Lymphadenopathie oder Beteiligung extranodaler Lokalisationen, falls ineligibel for Lokaltherapie.

    Für gastrische MALT Lymphome:
    Für gastrische MALT Lymphome ist der klinische Nachweis des MZL durch Gastroendoskopie ausreichend. Es muss keine messbare Läsion im CT oder MRT gezeigt werden. Siehe auch Appendix D.
    Patienten können eingeschlossen werden bei:
    – H. pylori-negativem Befall de novo oder nach Lokaltherapie oder ineligibel für Lokaltherapie (d.h. Operation, Strahlentherapie oder Antibiotika) oder systemischer Therpaie
    - H. pylori-positivem Befall der nach antibiotischer Therapie stabil bleibt, sich verschlechtert oder rezidiviert.
    E.4Principal exclusion criteria
    The presence of any of the following will exclude a subject from enrolment:
    – ECOG performance status ≥ 2
    – History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥1 year prior to study enrolment visit, other Stage 1 or 2 cancer treated with a curative intent and currently in complete remission, for ≥3 years.
    – Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma.
    – Ongoing immunosuppressive therapy including corticosteroids (expection <4 weeks administered at a dose equivalent to ≤ 40 mg/day prednisone is allowed)
    – Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of study enrolment visit
    – Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
    – Ongoing alcohol or drug addiction
    – Breastfeeding or pregnancy
    – Treatment with any other investigational agent within 30 days or within 5 x the half-life (t1/2) of the investigational product, whichever is longer, or participating in another trial within 30 days prior to entering this study
    – Prior treatment with Copanlisib
    – Congestive heart failure > New York Heart Association (NYHA) class 2
    – Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
    – Myocardial infarction less than 6 months before start of test drug
    – Uncontrolled arterial hypertension despite optimal medical management
    – HbA1c> 8.5%
    – Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results.
    – History of anaphylaxis in association with previous administration of monoclonal antibodies.
    – Vaccination with a live vaccine within 28 days prior to start of therapy
    – Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
    – Non-healing wound, ulcer, or bone fracture
    – History or concurrent interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
    Das Vorhandensein eines der folgenden Kriterien bedingt einenStudienausschluss:
    – ECOG Status ≥ 2
    – Anamnese eines nicht-lymphoiden Tumors mit Ausnahme der folgenden: adäquat behandelte lokale Basalzell- oder Plattenepithelkarzinome der Haut, zervikales Karzinom in situ, nicht invasives Blasenkarzinom, asymptomatisches Prostatakarzinom ohne Metastasen und ohne Therapiebedarf oder nur Notwendigkeit einer hormonellen Therapie mit normalem prostataspezifischem Antigen für ≥1 Jahr vor Studieneinschluss, andere behandelte Tumoren der Stadien 1 oder 2, die sich derzeit in vollständiger Remission befinden seit ≥3 Jahre
    – ZNS Lymphom, Meningeosis lymphomatosa oder histologischer Nachweis der Transformation in ein hochgradiges oder diffuses großzelliges B-Zell-Lymphom.
    – andauernde immunsuppressive Therapie einschließlich Kortikosteroide (Ausnahme: Verabreichung einer Dosis entsprechend ≤ 40 mg/Tag Prednison < 4 Wochen ist erlaubt)
    – Nachweis einer systemischen bakteriellen, Pilz- oder Virusinfektion zum Zeitpunkt des Studieneinschlusses
    – anhaltende medikamenteninduzierte Leberschädigung, chronische aktive Hepatitis B (HBV), alkoholische Lebererkrankung, nichtalkoholische Steatohepatitis, primäre biliäre Cholangitis, extrahepatische Cholestase durch Choledocholithiasis, Leberzirrhose oder portale Hypertension
    – Stillen oder Schwangerschaft
    – Behandlung mit einer anderen Studienmedikation innerhalb von 30 Tagen oder innerhalb 5 x der Halbwertszeit (t1/2) der Prüfsubstanz, was immer länger ist, oder Teilnahme an einer anderen Studie innerhalb von 30 Tagen vor Beginn der Studie
    – Vorherige Behandlung mit Copanlisib
    – Herzinsuffizienz > New York Heart Association (NYHA) Klasse 2
    – Instabile Angina (Angina Symptome in Ruhe), neu aufgetretene Angina (Beginn innerhalb der letzten 3 Monate).
    – Myokardinfrakt weniger als 6 Monate vor Studienmedikamenteneinnahme
    – Unkontrollierter arterieller Hypertonus trotz optimaler Blutdruckeinstellung
    – HbA1c> 8.5%
    – Abgelaufene oder aktuell klinisch bedeutsame Erkrankung, ein körperlicher Allgemeinzustand, eine Operationsanamnese, ein Elektrokardiogramm (EKG) Befund oder Laboranomalie, die nach Ansicht des Prüfers die Sicherheit des Patienten oder die Bewertung der Studienergebnisse beeinträchtigen könnte
    – Anamnese einer anaphylkatischen Reaktion, die in Verbindung mit der vorherigen Verabreichung von monoklonalen Antikörpern steht
    – Impfung mit einem Lebendimpfstoff innerhalb von 28 Tagen vor Therapiebeginn
    – Arterielle oder venöse Thromben wie kardiovaskuläre Ereignisse (einschließlich transitorisch ischämische Attacke), tiefe Venethrombose oder Lungenembolie innerhalb von 3 Monaten vor Studienbeginn
    – Nichtheilende Wunde, Ulzera oder Knochenfraktur
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoint:
    • CR rate (CRR) 12 months after start of treatment



    Primärer Endpunkt:
    • CR rate (CRR) 12 Monate nach Therapiebeginn



    E.5.1.1Timepoint(s) of evaluation of this end point
    Determined 12 months after start of induction therapy, i.e. month 6 of maintenance
    12 Monate nach Therapiebeginn
    E.5.2Secondary end point(s)
    Secondary Endpoints(s):
    • Response rate (CR, PR, CR or PR)
    • Best response
    • Time to best response
    • Time to first response
    • Progression free survival (PFS)
    • Time to treatment failure (TTF)
    • Duration of Response (DR)
    • Cause specific survival (CSS)
    • Overall survival (OS)
    • Quality of life during induction and maintenance therapy
    Sekundäre Endpunkte:
    • Gesamtansprechraten (CR, PR, CR oder PR)
    • Bestes Therapieansprechen
    • Zeit bis zum besten Therapieansprechen
    • Zeit bis zum ersten Therapieansprechen
    • Progressionsfreies Überleben
    • Zeit bis zum Behandlungsversagen
    • Remissionsdauer
    • Ursachenspezifisches Überleben
    • Gesamtüberleben
    • Lebensqualität während der Induktions- und Erhaltungstherapie
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 month after start of induction therapy, i.e. month 6 of maintenance and after end of study
    12 Monate nach Therapiebeginn und nach Beendigung der Studie
    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 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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 years10
    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 years10
    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: 16
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 56
    F.4.2.2In the whole clinical trial 56
    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 treatment is in the discretion of the treating physician
    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 German Lymphoma Alliance - GLA
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-09-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-08-09
    P. End of Trial
    P.End of Trial StatusOngoing
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