OPTIMAL>60 / DR. CHOP, Improvement of Therapy of Elderly Patients With CD20+ DLBCL Using Rituximab Optimized and Liposomal Vincristine (OPTIMAL>60)
CD20+ Aggressive B-Cell Lymphoma
About this trial
This is an interventional treatment trial for CD20+ Aggressive B-Cell Lymphoma focused on measuring DLBCL, Liposomal Vincristine (Marqibo), Optimised Rituximab, Toxicity, Elderly Patients, FDG-PET, Bulky Disease, Radiation, age >60 years, First line Therapy, Vitamin D
Eligibility Criteria
Inclusion Criteria:
- Age: 61-80 years
- All risk groups (IPI 1-5)
Diagnosis of aggressive CD20+ B-NHL, based on an excisional biopsy of a lymph node or on an appropriate sample of a lymph node or of an extranodal involvement. It will be possible to treat the following entities in this study as defined by the new WHO classification of 200870:
B-NHL:
- Foll. lymphoma grade IIIb
DLBCL, not otherwise specified (NOS)
common morphologic variants:
- centroblastic
- immunoblastic
- anaplastic
- rare morphologic variants
DLBCL subtypes/entities:
- T-cell/histiocyte-rich large B-cell lymphoma
- primary cutaneous DLBCL, leg type
- EBV-pos. DLBCL of the elderly
- DLBCL associated with chronic inflammation
- primary mediastinal (thymic) LBCL
- intravascular large B-cell-lymphoma
- ALK-positive large B-cell-lymphoma
- plasmoblastic lymphoma
- primary effusion lymphoma
- transformed indolent lymphoma secondary or simultaneous high grade B-cell-lymphoma
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
- B-cell lymphoma, unclassifiable, with features intermediate between DLCBL and Hodgkin lymphoma
- Performance status ECOG 0 - 2 after prephase treatment. The performance status of each patient must be assessed before the initiation and after the end of prephase treatment which, as experience has shown, can result in a significant improvement of the patient's performance status. The pre-treatment performance status which can range from ECOG 0 to ECOG 4 must be documented in the Staging CRF (see ISF); the performance status after the prephase treatment must be documented in the respective Prephase Treatment CRF (PT form: see ISF). A definition of the performance status is provided in Appendix 28.10.
- Written informed consent of the patient
- Contract of participation signed by the study centre and sponsor
Exclusion Criteria:
- Already initiated lymphoma therapy (except for the prephase treatment)
Serious accompanying disorder or impaired organ function (except when due to lymphoma involvement), in particular:
- heart: angina pectoris CCS >2, cardiac failure e.g. NYHA >2 and/or EF <50% or FS<25% in nuclear medicine examination/echocardiography
- lungs: if respiratory problems are suspected the patient is to be excluded if the resultant pulmonary function test shows FeV1<50% or a diffusion capacity <50% of the reference values
- kidneys: creatinine >2 times the upper reference limit
- liver: bilirubin >2 times the upper reference limit, aspartate transaminase (AST, SGOT) or alanine transaminase (ALT, SGPT) >3 x institutional upper reference limit
- uncontrollable diabetes mellitus (prephase treatment with predniso[lo]ne!)
- Platelets <75 000/mm3, leukocytes <2 500/mm3 (if not due to lymphoma)
- Known hypersensitivity to the medications to be used
- Known HIV-positivity
- Patients with severe impairment of immune defense
- Patients with constipation with imminent risk of ileus
- Chronic active hepatitis
- Poor patient compliance
- Simultaneous participation in other treatment studies or in another clinical trial within the last 6 months
- Prior chemo- or radiotherapy, long-term use of corticosteroids or anti-neoplastic drugs for previous disorder
- Other concomitant tumour disease and/or tumour disease in the past 5 years (except for localised skin tumors other than melanoma and carcinomas in situ of any other origin)
- CNS involvement of lymphoma (intracerebral, meningeal, intraspinal intradural) or primary CNS lymphoma
- Persistent neuropathy grade ≥2 (NCI CTC-AE v4.03) (unless due to lymphoma involvement)
- History of persistent active neurologic disorders grade >2 including demyelinating form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, or other demyelinating condition
- Pregnancy or breast-feeding women
- Active serious infections not controlled by oral and/or intravenous antibiotics or anti-fungal medication
- Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities.
- MALT lymphoma
- Non-conformity to eligibility criteria
- Persons not able to understand the impact, nature, risks and consequences of the trial (including language barrier)
- Persons not agreeing to the transmission of their pseudonymous data
- Persons depending on sponsor or investigator
- Persons from highly protected groups. Pts. with CNS lymphoma should not be included in this study.
Sites / Locations
- Saarland University Hospital
- Evangelisches Krankenhaus Paul Gerhardt Stift, Klinik für Innere Medizin II
- Klinik für Hämatologie und Onkologie
- Klinikum St. Marien Amberg, MVZ
- Klinikum Augsburg, Medizinische Klinik II
- Praxis Dres. med. Brudler, Heinrich, Bangerter
- Gemeinschaftspraxis Dres. Reichert, Janssen
- Helios Klinikum Bad Saarow, Klinik für Innere Medizin III
- Sozialstiftung Bamberg, Med. Klinik V
- Klinikum Bayreuth, Medizinische Klinik IV
- Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Med. Klinik III
- Knappschaftskrankenhaus Bochum
- Johanniter Krankenhaus Bonn, Abteilung für Innere Medizin I
- Universitätsklinikum Bonn, Med. Klinik III
- Städt. Klinikum Brandenburg, Med. Klinik II
- Evangelisches Diakonie-Krankenhaus Bremen
- Praxis Dr. Obst
- Praxis Dr. Marquard
- Klinikum Chemnitz, Innere Medizin III
- Klinikum Coburg, V. Med. Klinik
- Schwerpunktpraxis Dres. Glados/Retzlaff/Zühlsdorf/Deuticke
- St. Johannes Hospital Dortmund, Med. Klinik II
- BAG Freiberg-Richter, Jacobasch, Wolf, Illmer
- Gemeinschaftspraxis Dres. Mohm, Prange-Krex
- Universitätsklinikum Erlangen, Med. Klinik 5
- St.-Antonius-Hospital Eschweiler, Hämatologie und Onkologie
- Klinikum Esslingen, Klinik für Gastroenterologie, Onkologie und Innere Medizin
- Klinikum Frankfurt (Oder), Abteilung f. Innere Medizin
- Klinikum der J.W. Goethe-Universität Frankfurt, Hämatologie/Onkologie
- Krankenhaus Nordwest Frankfurt, II. Med. Klinik
- Praxis Dr. med. Reiber
- Universitätsklinikum Freiburg, Innere Medizin I
- Klinikum Fulda, Med. Klinik III
- St. Josef-Hospital Gelsenkirchen, Onkologie und Hämatologie
- Praxis Dr. med. Schliesser
- Wilhelm-Anton-Hospital Goch, Innere Medizin
- Onkologische Kooperation Harz, Onkologische Schwerpunktpraxis
- Universitätsmedizin Greifswald, Medizinische Universitätsklinik C, Hämatologie und Onkologie
- Kreiskrankenhaus Gummersbach
- Universitätsmedizin Göttingen, Hämatologie und Onkologie
- Klinikum Gütersloh
- Kath. Krankenhaus Hagen, St.-Marien-Hospital
- Gemeinschaftspraxis Rohrberg, Hurtz, Schmidt, Frank-Gleich
- Asklepios Klinik St. Georg, Hämatologie/Onkologie
- Hämatolog.-onkolog. Praxis Dres. Müller-Hagen, Bertram, Albertinen-Krankenhaus
- Hämatologisch-onkologische Praxis Altona (HOPA)
- Universitätsklinikum Hamburg-Eppendorf (UKE), II. Med. Klinik und Poliklinik, Onkologie und Hämatologie
- Klinikum Hannover-Siloah, Klinik für Hämatologie
- Medizinische Hochschule Hannover (MHH), Zentrum für Innere Medizin, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
- Praxis MediProjekt
- Universitätsklinikum Heidelberg, Innere Medizin V
- Klinikum Kreis Herford, Med. Klinik II
- Onkologische Schwerpunktpraxis Dres. Freier, Sievers
- St. Bernward Krankenhaus Hildesheim, Med. Klinik II
- KMT Klinik Idar-Oberstein
- Universitätsklinikum Jena, Klinik für Innere Medizin II
- Westpfalz-Klinikum, Klinik für Innere Medizin I
- Praxis Dres Hansen, Reeb
- St. Vincentius Kliniken Karlsruhe, Med. Klinik Abt. 2
- Städtisches Klinikum Karlsruhe, II. Med. Klinik, Hämatologie/Onkologie/Infektionskrankheiten
- GMP Dres Siehl, Söling
- Rotes Kreuz Krankenhaus Kassel, Klinik für Interdisziplinäre Onkologie
- Klinikum Kempten-Oberallgäu, Hämatologie, Onkologie und Palliativmedizin
- Gemeinschaftsklinikum Mittelrhein, Ev. Stift St. Martin, Innere Medizin
- Gemeinschaftspraxis Dres. Neise, Lollert
- Praxis Dr. Strauch
- Gemeinschaftspraxis Dres. Schmitz, Steinmetz, Severin
- Klinikum der Universität zu Köln, Klinik I für Innere Medizin
- Krankenhaus Holweide
- Klinikum Landshut, Med. Klinik I
- Caritas Krankenhaus Lebach
- Onkologische Schwerpunktpraxis
- Klinikum St. Georg Leipzig, Abteilung für internistische Onkologie/Hämatologie
- Klinikum Lippe-Lemgo, Med. Klinik II
- Onkologische Schwerpunktpraxis Lörrach
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck
- Klinikum Magdeburg, Hämatologie/Onkologie
- Universitätsmedizin Mainz, III. Med. Klinik und Poliklinik
- Mannheimer Onkologie Praxis, Dres. Brust, Plöger, Schuster, Hensel
- Universitätsklinikum Gießen und Marburg
- Johannes Wesling Klinikum, Klinik für Hämatologie, Onkologie und Palliativmedizin
- Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin
- Kliniken Maria-Hilf Mönchengladbach, Innere Medizin I
- GMP Dres Schröder/Sieg
- Praxis Dres. Schmidt, Fromm, Wiesmeier, Seufert, Klapthor, Zingerle
- Klinikum Großhadern, Med. Klinik 3
- Klinikum rechts der Isar der Technischen Universität München, III. Med.Klinik
- Städtisches Klinikum München Harlaching
- Universitätsklinikum Münster, Med. Klinik A
- Onkologische Praxis Dr. Ladda
- Lukaskrankenhaus Neuss, Med. Klinik II
- Kreiskliniken Esslingen, Klinikum Kirchheim-Nürtingen, Hämatologie, Internist. Onkologie und Palliativmedizin
- Gemeinschaftspraxis Dres. Balló, Böck
- Ortenau Klinikum Offenburg-Gegenbach, Medizinische Klinik II
- Klinikum Oldenburg, Hämatologie/Onkologie
- Onkologische Schwerpunktpraxis Dr. Hübner
- Pius Hospital Oldenburg, Klinik für Strahlentherapie und Internistische Onkologie
- Onkologische Schwerpunktpraxis im MVZ 2 GmbH, Dr. H. Eimermacher
- Klinikum Osnabrück, Med. Klinik III
- Paracelsus Krankenhaus Ruit, Kreiskliniken Esslingen gGmbH, Zentrum für Allgemeine Innere Medizin
- Brüderkrankenhaus St. Josef Paderborn, Klinik für Hämatologie und Onkologie
- Gemeinschaftspraxis Dres. Baake, Leonhardt, Moegling, am Regio Klinikum Pinneberg
- Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie und Palliativmedizin
- Gemeinschaftspraxis Dres. Decker, Nonnenbroich, Herbrik-Zipp
- Prosper-Hospital Recklinghausen, Med. Klinik I
- Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
- Klinikum am Steinenberg, Kreiskliniken Reutlingen GmbH
- Elblandklinikum Riesa, Klinik für Innere Medizin II
- Klinikum Südstadt Rostock, Innere Medizin
- Universitätsklinikum Rostock, Abteilung Hämatologie/Onkologie, Klinik u. Poliklinik für Innere Medizin
- GMP Dres Jacobs, Daus, Schmits
- ZAHO-Siegburg, Zentrum für ambulante Hämatologie und Onkologie Siegburg
- Diakonie-Klinikum Stuttgart, Med. Klinik II
- Klinikum Traunstein, Hämatologie/Onkologie
- Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I
- Krankenhaus der Barmherzigen Brüder Trier, I. Med. Abteilung
- Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik, Onkologie, Hämatologie, Immunologie und Rheumatologie
- Universitätsklinikum Ulm, Innere Medizin III
- Katharinen Hospital Unna
- Schwarzwald-Baar-Klinikum - Innere Medizin II
- Praxis Onkologie Schwarzwald - Alb
- Med. Versorgungszentrum Weiden, Abteilung für Onkologie
- Praxis Dres med. Perker, Sandherr
- HSK Wiesbaden, Innere Medizin III
- Helios Klinkum Wuppertal, Med. Klinik I
- Hämatologisch-Onkologische Praxis Würselen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Active Comparator
Experimental
Active Comparator
Experimental
Experimental
Experimental
Favourable Prognosis F-A - Recruitment completed
Favourable F-B - Arm Closed
Less Favourable LF-A - Recruitment completed
Less Favourable LF-B - Recruitment completed
Less Favourable LF-C - Recruitment completed
Less Favourable LF-D - Recruitment completed
Induction therapy with 4 cycles of R-CHOP-14 (Rituximab 375 mg/sqm, Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, conventional Vincristine 1,4 mg/sqm [max. 2mg absolute], Predniso[lo]ne 100mg/d d1-5) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive 2 additional cycles of R-CHOP-14 + 2xR plus additional involved-site radiotherapy, if FDG-PET negative only 4xR without radiotherapy.
Induction therapy with 4 cycles of R-CHLIP-14 (Rituximab 375 mg/sqm, Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, liposomal Vincristine 1,4 mg/sqm (max. 2mg absolute), Predniso[lo]ne 100mg/d d1-5) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive 2 additional cycles of R-CHLIP-14 + 2xR plus additional involved-site radiotherapy, if FDG-PET negative only 4xR without radiotherapy.
Induction therapy with 6 cycles of R-CHOP-14 (Rituximab 375 mg/sqm, Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, conventional Vincristine 1,4 mg/sqm [max. 2mg absolute], Predniso[lo]ne 100mg/d d1-5) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive 2xR plus additional radiotherapy to the initial bulky region, if FDG-PET negative only 2xR without radiotherapy. After 3xR-CHOP-14 an interim restaging will be performed.
Induction therapy with 6 cycles of R-CHLIP-14 (Rituximab 375 mg/sqm, Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, liposomal Vincristine 1,67 mg/sqm [uncapped], , Predniso[lo]ne 100mg/d d1-5) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive 2xR plus additional radiotherapy to the initial bulky region, if FDG-PET negative only 2xR without radiotherapy. After 3xR-CHLIP-14 an interim restaging will be performed. Recruitment completed.
Induction therapy with 6 cycles of CHOP-14 (Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, conventional Vincristine 1,4 mg/sqm [max. 2mg absolute], Predniso[lo]ne 100mg/d d1-5) combined with an optimized Rituximab-schedule (375 mg/sqm, d-4, d-1, d1, d4, d14, d28, d42, d56, d91, d126, d175, d238) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive additional radiotherapy to the initial bulky region, if FDG-PET negative omission of radiotherapy. After 3x CHOP-14 an interim restaging will be performed. Recruitment completed.
Induction therapy with 6 cycles of CHLIP-14 (Cyclophosphamide 750 mg/sqm, Doxorubicin 50 mg/sqm, 1,67 mg/sqm [uncapped], , Predniso[lo]ne 100mg/d d1-5) combined with an optimised Rituximab-schedule (375 mg/sqm, d-4, d-1, d1, d4, d14, d28, d42, d56, d91, d126, d175, d238) and then definitive (post-induction) restaging with FDG-PET. If FDG-PET positive additional radiotherapy to the initial bulky region, if FDG-PET negative omission of radiotherapy. After 3x CHLIP-14 an interim restaging will be performed. Recruitment completed.