JOURNAL ONKOLOGIE – STUDIE

ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT02858258

Studienbeginn:
Juli 2016

Letztes Update:
19.12.2017

Wirkstoff:
R-CHOP/R-DHAP, Ibrutinib (Induction), ASCT conditioning, Ibrutinib (Maintenance)

Indikation (Clinical Trials):
Lymphoma, Lymphoma, Mantle-Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Prof. Dr. M. Dreyling (co-chairman)

Collaborator:
LMU Klinikum

Studienleiter

Martin Dreyling, Prof.
Principal Investigator
Klinikum der Universität München

Kontakt

Döndü Gözel
Kontakt:
Phone: +49 89 4400
Phone (ext.): 77906
E-Mail: Doendue.Goezel@med.uni-muenchen.de» Kontaktdaten anzeigen

Christian Schmidt, Dr.
Kontakt:
Phone: +49 89 4400
Phone (ext.): 74900
E-Mail: Christian_Schmidt@med.uni-muenchen.de» Kontaktdaten anzeigen

Studienlocations
(3 von 112)

Zentralklinik Augsburg, II. Med. Klinik, Hämatologie int. Onkologie
86156 Augsburg
(Bayern)
GermanyRekrutierend» Google-Maps

Onkologische Gemeinschaftspraxis Dr. Janssen/Dr. Reichert in der Ubbo-Emmius-Klinik
26603 Aurich
(Niedersachsen)
GermanyRekrutierend» Google-Maps

Klinikum Bayreuth, Klinik f. Onkologie und Hämatologie
95445 Bayreuth
(Bayern)
GermanyRekrutierend» Google-Maps

Vivantes Klinikum Am Urban, Klinik f. Innere Medizin, Hämatologie und Onkologie
10967 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps

Charité Univ.-Medizin Berlin, Med. Klinik - Hämatologie, Onkologie und Tumorimmunologie
12200 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps

Helios Klinikum Berlin-Buch, Hämatologie, Onkologie und Tumorimmunologie
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps

Knappschaftskrankenhaus Bochum-Langendreer
44892 Bochum
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Bonn
53127 Bonn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Diako ev. Diakonie-KH gGmbH, Med. Klinik II, Hämatologie und Onkologie
28239 Bremen
(Bremen)
GermanyRekrutierend» Google-Maps

Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin II
09113 Chemnitz
(Sachsen)
GermanyRekrutierend» Google-Maps

DONAUISAR Klinikum Deggendorf, Innere Medizin II
94469 Deggendorf
(Bayern)
GermanyRekrutierend» Google-Maps

St.-Johannes-Hospital
44137 Dortmund
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Gemeinschaftspraxis Dr. Mohm und Prange-Krex - Fachärzte für Innere Medizin und Hämatologie und Onkologie
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Düsseldorf, Klinik f. Hämatologie, Onkologie und klinische Immunologie
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Brustkrebszentrum am Marien Hospital Düsseldorf
Rochusstraße 2
40479 Düsseldorf
DeutschlandRekrutierend» Google-Maps

Helios Klinikum Erfurt GmbH, Zentrum f. Innere Medizin u. internistische Onkologie, Hämostaseologie
99089 Erfurt
(Thüringen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Erlangen, Med. Klinik 5, Hämatologie und internistische Onkologie
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps

St.-Antonius-Hospital Eschweiler, Klinik für Hämatologie und Onkologie
52249 Eschweiler
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Essen, Klinik f. Hämatologie
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Freiburg, Klinik f. Innere Medizin, Hämatologie, Onkologie u. Stammzelltransplantation
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Universitätsmedizin Greifswald, Klinik u. Poliklinik f. Innere Medizin C, Hämatologie u. Onkologie-, Transplantationszentrum
17475 Greifswald
(Mecklenburg-Vorpommern)
GermanyRekrutierend» Google-Maps

Universitätsmedizin Göttingen, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Medizinische Onkologie
37075 Göttingen
(Niedersachsen)
GermanyRekrutierend» Google-Maps

Katholisches Krankenhaus Hagen gGmbH, St.-Marien-Hospital, Klinik f. Hämatologie und Onkologie
58095 Hagen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Hamburg-Eppendorf (UKE), II. Med. Klinik u. Poliklinik, Onkologie, Hämatologie, KMT
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps

Asklepios Klinik Altona, II. Med.Abt. f. Hämatologie und internistische Onkologie, Stammzelltransplantation
22763 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Heidelberg, Med. Klinik - Innere Medizin V - Hämatologie, Onkologie und Rheumatologie
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Universitätsklinikum des Saarlandes, Klinik f. Innere Medizin I Hämatologie & Onkologie
66421 Homburg
(Saarland)
GermanyRekrutierend» Google-Maps

Klinikum Idar-Oberstein GmbH, Medizinische Klinik I
55743 Idar-Oberstein
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Universitätsmedizin Jena, Klinik f. Innere Medizin II, Abteilung Hämatologie u. Internistische Onkologie
07747 Jena
(Thüringen)
GermanyRekrutierend» Google-Maps

Städtisches Klinikum Karlsruhe, Med. Klinik III, Hämatologie und Onkologie
76133 Karlsruhe
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik f. Innere Medizin II - Hämatologie und Onkologie
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps

Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Klinik f. Innere Medizin
56068 Koblenz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Praxisklinik f. Hämatologie und Onkologie Koblenz
56068 Koblenz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Uniklinik Köln, Klinik I für Innere Medizin
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Onkologisch-Hämatologische Praxis Dr. Vehling-Kaiser
84028 Landshut
(Bayern)
GermanyRekrutierend» Google-Maps

Klinikum Landshut gGmbH, Med. Klinik III, Hämatologie/Internistische Onkologie
84034 Landshut
(Bayern)
GermanyRekrutierend» Google-Maps

Caritas-KHLebach, Gemeinschaftspraxis f. Hämatologie und Onkologie, Onkologisches Zentrum Lebach
66822 Lebach
(Saarland)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Leipzig AöR, selbständige Abteilung f. Hämatologie und Internistische Onkologie, Hämostaseologische Ambulanz
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps

Klinikum Lippe GmbH, Onkologie und Hämatologie
32657 Lemgo
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Med. Klinik A
67063 Ludwigshafen
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Magdeburg AöR, Klinik f. Hämatologie und Onkologie
39120 Magdeburg
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps

Universitätsmedizin der Univ. Mainz, III. Med. Klinik u. Poliklinik
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Johannes Wiesling Klinikum Minden, Klinik f. Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin
32429 Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Klinikum der Universität München, Med. Klinik und Poliklinik III
81377 München
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christian Schmidt, Dr.
E-Mail: Christian_Schmidt@med.uni-muenchen.de» Ansprechpartner anzeigen

Klinikum Rechts der Isar, III. Med. Klinik - Hämatologie und Onkologie
81675 München
(Bayern)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Münster, Med. Klinik A, Translationale Onkologie / Lymphome
48149 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Klinikum Nürnberg,5. Medizinische Klinik, Onkologie / Hämatologie
90419 Nürnberg
(Bayern)
GermanyRekrutierend» Google-Maps

Klinikum Oldenburg gGmbH, Med. Klinik II
26133 Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps

Klinikum Ernst von Bergmann Potsdam gGmbH, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Onkologie
14467 Potsdam
(Brandenburg)
GermanyRekrutierend» Google-Maps

KH Barmherzige Brüder, Klinik f. Onkologie und Hämatologie
93049 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps

Universitätsmedizin Rostock, Abt. f. Hämatologie und Onkologie, Klinik und Poliklinik für Innere Medizin
18057 Rostock
(Mecklenburg-Vorpommern)
GermanyRekrutierend» Google-Maps

Klinikum Stuttgart - Katharinenhospital, Klinik f. Hämatologie und Onkologie
70174 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Robert-Bosch-Krankenhaus, Abt.f. Hämatologie und Onkologie
70376 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Klinikum Traunstein, Hämatologie - Onkologie- Palliativmedizin
83278 Traunstein
(Bayern)
GermanyRekrutierend» Google-Maps

Klinikum Mutterhaus der Borromäerinnen gGmbH, Okologisches Zentrum
54290 Trier
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Tübingen, Med Klinik I, Innere Medizin II
72026 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Ulm, Klinik für Innere Medizin III
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Klinikum Wolfsburg, Med. Klinik II
38440 Wolfsburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Würzburg, Med. Klinik u. Poliklinik II /ZIM
97080 Würzburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps

Aalborg University Hospital, Dept of Hematology
9000 Aalborg
DenmarkNoch nicht rekrutierend» Google-Maps

Aarhus University Hospital, Dept of Hematology
8000 Aarhus C
DenmarkNoch nicht rekrutierend» Google-Maps

Rigshospitalet, Clinic of Hematology
2100 Copenhagen
DenmarkNoch nicht rekrutierend» Google-Maps

Herlev Hospital, Department of Hematology L121
2730 Herlev
DenmarkNoch nicht rekrutierend» Google-Maps

Odense University Hospital, Dept of Hematology X
5000 Odense C
DenmarkNoch nicht rekrutierend» Google-Maps

Sjaelland University Hospital, Dept of Hematology
4000 Roskilde
DenmarkNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo, SC Ematologia
15121 Alessandria
ItalyRekrutierend» Google-Maps

Policlinico S. Orsola Malpighi, Istituto di Ematologia e Oncologia Medica Seragnoli
40138 Bologna
ItalyNoch nicht rekrutierend» Google-Maps

Comprensorio Sanitario di Bolzano, Ematologia e trapianto di midollo osseo
39100 Bolzano
ItalyNoch nicht rekrutierend» Google-Maps

Spedali Civili, Struttura Complessa di Ematologia
25123 Brescia
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale Businco, UO Ematologia - CTMO
09121 Cagliari
ItalyNoch nicht rekrutierend» Google-Maps

ASO S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
12100 Cuneo
ItalyNoch nicht rekrutierend» Google-Maps

AOU Policlinico Careggi, Unità Funzionale di Ematologia
50134 Firenze
ItalyNoch nicht rekrutierend» Google-Maps

IRCCS AOU S. Martino - IST, Clinica Ematologia
16132 Genova
ItalyNoch nicht rekrutierend» Google-Maps

IRCCS AOU S. Martino - IST, Ematologia
16132 Genova
ItalyNoch nicht rekrutierend» Google-Maps

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Ematologia
47014 Meldola (FC)
ItalyNoch nicht rekrutierend» Google-Maps

Istituto Scientifico San Raffaele, Unità Ricerca Clinica Linfomi
20132 Milano
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale Niguarda, Struttura Complessa di Ematologia
20162 Milano
ItalyNoch nicht rekrutierend» Google-Maps

Università di Modena e Reggio Emilia Policlinico - COM Centro Oncologico Modenese, Dipartimento di Oncologia ed Ematologia
41124 Modena
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale S. Gerardo, Divisione di Ematologia
20052 Monza
ItalyNoch nicht rekrutierend» Google-Maps

"IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale", Ematologia Oncologica
80131 Napoli
ItalyRekrutierend» Google-Maps

AOU Maggiore della Carità - Università del Piemonte Orientale, S.C.D.U Ematologia
28100 Novara
ItalyNoch nicht rekrutierend» Google-Maps

AO Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
90146 Palermo
ItalyNoch nicht rekrutierend» Google-Maps

IRCCS Fondazione Policlinico San Matteo, Clinica Ematologia
27100 Pavia
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliera Pisana Ospedale "S.Chiara", Dipartimento di Oncologia Divisione di Ematologia
56126 Pisa
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale S. Maria delle Croci, U.O di Ematologia
48121 Ravenna
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliera Bianchi, Melacrino, Morelli, Divisione di Ematologia
89125 Reggio Calabria
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Ematologia
42123 Reggio Emilia
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale degli Infermi, U.O. Ematologia
47923 Rimini
ItalyNoch nicht rekrutierend» Google-Maps

Policlinico Tor Vergata, UOC Oncoematologia
00133 Roma
ItalyNoch nicht rekrutierend» Google-Maps

Università La Sapienza, Ematologia
00161 Roma
ItalyNoch nicht rekrutierend» Google-Maps

Casa Sollievo della Sofferenza, U.O. Ematologia
71013 San Giovanni Rotondo
ItalyNoch nicht rekrutierend» Google-Maps

A.O. Città della Salute e della Scienza, SC Ematologia
10126 Torino
ItalyNoch nicht rekrutierend» Google-Maps

A.O. U. Città della Salute e della Scienza, S C Ematologia U
10126 Torino
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale Cà Foncello, U.O.C. Ematologia
31100 Treviso
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale Cardinale Panico, Divisione di Ematologia
73054 Tricase
ItalyNoch nicht rekrutierend» Google-Maps

ASUI Integrata di Udine, Clinica Ematologia
33100 Udine
ItalyNoch nicht rekrutierend» Google-Maps

Ospedale Policlinico G.B. Rossi, "Centro trapianto midollo osseo Ematologia"
37134 Verona
ItalyRekrutierend» Google-Maps

Ospedale S. Bortolo, Ematologia
36100 Vicenza
ItalyRekrutierend» Google-Maps

Haukeland University Hospital , Dept. of Oncology and Medical Physics
5021 Bergen
NorwayNoch nicht rekrutierend» Google-Maps

Oslo University Hospital, Dept of Oncology
0310 Oslo
NorwayNoch nicht rekrutierend» Google-Maps

Stavanger University Hospital, Division for Hematology&Oncology
4011 Stavanger
NorwayNoch nicht rekrutierend» Google-Maps

UNN Tromsø, Oncology Dep
9038 Tromsø
NorwayNoch nicht rekrutierend» Google-Maps

St. Olavs Hospital, Department of Oncology
7006 Trondheim
NorwayNoch nicht rekrutierend» Google-Maps

Sahlgrenska University Hospital, Section of Hematology and Coagulation, Dept of internal medicine
413 45 Göteborg
SwedenNoch nicht rekrutierend» Google-Maps

University Hospital, Dept of Hematolgy
581 85 Linköping
SwedenRekrutierend» Google-Maps

Sunderbyn Hospital, Dept of Medicine
971 80 Lulea
SwedenNoch nicht rekrutierend» Google-Maps

Skane University Hospital
221 85 Lund
SwedenRekrutierend» Google-Maps
Ansprechpartner:
Mats Jerkeman, MD» Ansprechpartner anzeigen

Karolinska University Hospital, Center of Hematology
141 86 Stockholm
SwedenRekrutierend» Google-Maps

Norrland University Hospital, Dept of Oncology
901 85 Umea
SwedenNoch nicht rekrutierend» Google-Maps

Academic Hospital, Dept of Oncology
751 85 Uppsala
SwedenRekrutierend» Google-Maps

Örebro University Hospital, Dept of Oncology
701 85 Örebro
SwedenRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

Objectives and Endpoints

Primary Objective:

To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A),

R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I),

and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm I) as future

standard based on the comparison of the investigator-assessed failure-free survival (FFS).

Secondary Objectives:

- To compare the efficacy of the three treatment arms in terms of secondary efficacy

endpoints

- To determine the safety and tolerability of ibrutinib during induction

immuno-chemotherapy and during maintenance and to compare the safety profile of the

three treatment arms in terms of secondary toxicity endpoints

Primary Endpoint:

FFS defined as time from start of treatment to stable disease at end of immuno-chemotherapy,

progressive disease, or death from any cause.

Secondary Efficacy Endpoints:

- Overall survival (OS)

- Progression-free survival (PFS) from randomization, from end of induction

immuno-chemotherapy in patients with CR or PR at end of induction immuno-chemotherapy,

and from the staging 6 weeks after end of induction assessment (at month 6)

- Overall response and complete remission rates at midterm, at end of induction, 3 months

after end of induction immunochemotherapy (at month 6)

- PR to CR conversion rate during follow-up after end of induction immuno-chemotherapy

Secondary Toxicity Endpoints:

- Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction

immuno-chemotherapy and during periods of follow-up after response to

immune-chemotherapy

- Cumulative incidence rates of SPMs

Exploratory Objectives:

- To compare feasibility of ASCT in arm A+I vs. arm A

- To compare minimal residual disease status between the three treatment groups

- To determine the impact of ibrutinib during induction immuno-chemotherapy and during

maintenance therapy on the minimal residual disease status

- To determine the prognostic value of minimal residual disease status

- To determine the prognostic value of positron emission tomography with fluorine

18-fluorodeoxyglucose

- To determine clinical and biological prognostic and predictive factors

- To determine the role of total body irradiation (TBI) in ASCT conditioning

Exploratory Endpoints:

- Rate of successful stem cell mobilisations (success: separation of at least 2x2x10(6)

CD34-positive cells, including a back-up)

- Rate of molecular remissions (MRD-negative patients) at midterm, at end of induction

immuno-chemotherapy, and at staging time-points during follow-up in patients with

remission after end of induction immuno-chemotherapy

- Time to molecular remission from start of therapy

- Time to molecular relapse for patients in clinical and molecular remission after end of

induction immunochemotherapy

- RD in FDG-PET negative or positive patients after induction and ASCT

Exploratory objectives may be evaluated only in a subset of patients according to local

standards and resources.

Ein-/Ausschlusskriterien

Inclusion Criteria:

All patients must meet the following criteria:

- Histologically confirmed diagnosis of MCL according to WHO classification

- suitable for high-dose treatment including high-dose Ara-C

- Stage II-IV (Ann Arbor)

- Age ≥ 18 years and ≤ 65 years

- Previously untreated MCL

- At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow

aspiration and biopsy is mandatory for all staging evaluations.

- ECOG/WHO performance status ≤ 2

- The following laboratory values at screening (unless related to MCL):

- Absolute neutrophil count (ANC) ≥1000 cells/µL

- Platelets ≥100,000 cells/µL

- Transaminases (AST and ALT) ≤3 x upper limit of normal (ULN)

- Total bilirubin ≤2 x ULN unless due to known Morbus Meulengracht

[Gilbert-Meulengracht-Syndrome])

- Creatinine ≤2 mg/dL or calculated creatinine clearance ≥ 50 mL/min

- Written informed consent form according to ICH/EU GCP and national regulations

- Sexually active men and women of child-bearing potential must agree to use highly

effective contraceptives (eg, condoms, implants, injectables, combined oral

contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while

on study; this should be maintained for 90 days after the last dose of study drug.

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from

participating in the study.

- Major surgery within 4 weeks prior to randomization.

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg

phenprocoumon).

- History of stroke or intracranial hemorrhage within 6 months prior to randomization.

- Requires treatment with strong CYP3A4/5 inhibitors.

- Any life-threatening illness, medical condition, or organ system dysfunction which, in

the investigator's opinion, could compromise the subject's safety, interfere with the

absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue

risk.

- Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.

- Known CNS involvement of MCL

- Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions

to the compound of ibrutinib itself or to the excipients in its formulation)

- Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine

antibodies

- Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or

interferon except prephase therapy according to trial protocol

- Serious concomitant disease interfering with a regular therapy according to the study

protocol:

- Cardiac (Clinically significant cardiovascular disease such as uncontrolled or

symptomatic arrhythmias, congestive heart failure, or myocardial infarction

within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe)

cardiac disease as defined by the New York Heart Association Functional

Classification or LVEF below LLN )

- Pulmonary (e.g. chronic lung disease with hypoxemia)

- Endocrinological (e.g. severe, not sufficiently controlled diabetes mellitus)

- Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value

and/or creatinin clearance < 50 ml/min)

- Impairment of liver function (unless caused by the lymphoma): transaminases > 3x

normal or bilirubin > 2,0 mg/dl unless due to morbus Meulengracht

(Gilbert-Meulengracht-Syndrome)

- Patients with unresolved hepatitis B or C infection or known HIV positive infection

(mandatory test)

- Prior organ, bone marrow or peripheral blood stem cell transplantation

- Concomitant or previous malignancies within the last 3 years other than basal cell

skin cancer or in situ uterine cervix cancer

- Pregnancy or lactation

- Any psychological, familiar, sociological, or geographical condition potentially

hampering compliance with the study protocol and follow up schedule

- Subjects not able to give consent

- Subjects without legal capacity who are unable to understand the nature, scope,

significance and consequences of this clinical trial

- Participation in another clinical trial within 30 days before randomization in this

study.

Studien-Rationale

Primary outcome:

1. Failure Free Survival (Time Frame - From start of treatment until stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause, whichever comes first, assessed up to 120 months.)

Secondary outcome:

1. Overall Survival (Time Frame - From start of treatment until the date of first documented progression, assessed up to 120 months.)

2. Number of participants with treatment-related adverse events as assessed by CTC Version 4.03 (Time Frame - From start of Ibrutinib treatment during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints. Through study conduction, an average of up to 30 months.):
Safety and tolerability

3. Progression-free survival (PFS) (Time Frame - PFS is the time to progression or death from any cause. Assed up to 120 months.)

4. Number of Secondary Primary Malignancies (Time Frame - From start of treatment through the study conduction, up to 120 months.):
Toxicity Endpoints

5. Number of Adverse Events by CTC grade (Version 4.03) (Time Frame - From start of treatment through the study conduction, up to 120 months.):
Toxicity Endpoints

Studien-Arme

Active Comparator: Standard Arm A
R-CHOP/R-DHAP: Alternating 3 cycles of R-CHOP in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM
Experimental: Experimental Arm A+I
R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace)
Experimental: Experimental Arm I
R-CHOP+Ibrutinib / R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenance)

Geprüfte Regime

R-CHOP/R-DHAP (rituximab, CHOP, DHAP):
Drug: R-CHOP/DHAP Alternating 3x R-CHOP (Rituximab , Cyclophosphamide ,Doxorubicine ,Vincristine , Prednisone) / 3x R-DHAP (Rituximab , Dexamethasone, Ara-C, Cisplatine, G-CSF)
Ibrutinib (Induction) (Imbruvica):
Ibrutinib: only in cycle 1,3,5 on Day 1-19
ASCT conditioning (THAM or BEAM):
ASCT conditioning THAM or BEAM, stratified per site before trial activation at site THAM (TBI (total body irradiation), Ara-C, Melphalan) or BEAM (BCNU, Etoposide, Cytarabine, Melphalan)
Ibrutinib (Maintenance) (Imbruvica):
Ibrutinib (Maintenance), daily 560 mg for 2 years;

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma"

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