OPTIMAL>60 / DR. CHOP, Improvement of Therapy of Elderly Patients with CD20+ DLBCL Using Rituximab Optimized and Liposomal Vincristine
OPTIMAL>60
Improvement of Outcome and Reduction of Toxicity in Elderly Patients with CD20+ Aggressive B-Cell Lymphoma by an Optimised Schedule of the Monoclonal Antibody Rituximab, Substitution of Conventional by Liposomal Vincristine, and FDG-PET Based Reduction of Therapy in Combination with Vitamin D Substitution
1 other identifier
interventional
1,152
1 country
127
Brief Summary
The purpose of this study is to improve the outcome of elderly patients with CD20-Aggressive B-Cell Lymphoma and to reduce the toxicity of standard used Immuno-Chemotherapy by using an optimised schedule of the monoclonal antibody Rituximab, substituting conventional by Liposomal Vincristine and by a PET-guided reduction of therapy in Combination with Vitamin D Substitution.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2011
Longer than P75 for phase_3
127 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2011
CompletedFirst Submitted
Initial submission to the registry
November 18, 2011
CompletedFirst Posted
Study publicly available on registry
November 23, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 18, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 18, 2024
CompletedJanuary 8, 2025
January 1, 2025
12.2 years
November 18, 2011
January 6, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival
"OPTIMAL\>60 Less Favourable": To test the effects of substitution of conventional by liposomal vincristine and of a 2-week applications of 8x rituximab by an optimised application of 12 x rituximab stratified log rank tests will be performed for each question (stratified for IPI-factors). Proportional hazard models will be used to investigate treatment interaction and to obtain estimates for the single treatment effects (HR) adjusting for the IPI-factors. "OPTIMAL\>60 Favourable" Grade of neurotoxicity will be estimated and indicated with a 95% confidence interval (CI) separated to each type of vincristine. To investigate the 3-year PFS with 95% CI the Kaplan-Meier estimator will be used.
9 years
Secondary Outcomes (1)
for efficacy: CR-rate, PR-rate, rate of primary progressions, relapse rate, EFS and OS; rate and CTC grades of PNP. Prognostic value of the FDG-PET derived imaging biomarkers for lymphoma load: SUV, MTV, TLG.
9 years
Study Arms (6)
Favourable Prognosis F-A - Recruitment completed
ACTIVE COMPARATORInduction 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.
Favourable F-B - Arm Closed
EXPERIMENTALInduction 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.
Less Favourable LF-A - Recruitment completed
ACTIVE COMPARATORInduction 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.
Less Favourable LF-B - Recruitment completed
EXPERIMENTALInduction 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.
Less Favourable LF-C - Recruitment completed
EXPERIMENTALInduction 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.
Less Favourable LF-D - Recruitment completed
EXPERIMENTALInduction 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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
- +12 more criteria
You may not qualify if:
- 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
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Universität des Saarlandeslead
- German High-Grade Non-Hodgkin's Lymphoma Study Groupcollaborator
- Spectrum Pharmaceuticals, Inccollaborator
Study Sites (127)
Saarland University Hospital
Homburg, Saarland, 66421, Germany
Evangelisches Krankenhaus Paul Gerhardt Stift, Klinik für Innere Medizin II
Wittenberg, Saxony-Anhalt, 06886, Germany
Klinik für Hämatologie und Onkologie
Aachen, 52074, Germany
Innklinikum Altötting
Altötting, 84503, Germany
Klinikum St. Marien Amberg, MVZ
Amberg, Germany
Klinikum Augsburg, Medizinische Klinik II
Augsburg, Germany
Praxis Dres. med. Brudler, Heinrich, Bangerter
Augsburg, Germany
Gemeinschaftspraxis Dres. Reichert, Janssen
Aurich, Germany
Helios Klinikum Bad Saarow, Klinik für Innere Medizin III
Bad Saarow, Germany
Sozialstiftung Bamberg, Med. Klinik V
Bamberg, Germany
Klinikum Bayreuth, Medizinische Klinik IV
Bayreuth, Germany
Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Med. Klinik III
Berlin, Germany
Knappschaftskrankenhaus Bochum
Bochum, Germany
Johanniter Krankenhaus Bonn, Abteilung für Innere Medizin I
Bonn, Germany
Universitätsklinikum Bonn, Med. Klinik III
Bonn, Germany
Städt. Klinikum Brandenburg, Med. Klinik II
Brandenburg, Germany
Evangelisches Diakonie-Krankenhaus Bremen
Bremen, Germany
Praxis Dr. Obst
Burgwedel, Germany
Praxis Dr. Marquard
Celle, Germany
Klinikum Chemnitz, Innere Medizin III
Chemnitz, Germany
Klinikum Coburg, V. Med. Klinik
Coburg, Germany
Schwerpunktpraxis Dres. Glados/Retzlaff/Zühlsdorf/Deuticke
Coesfeld, Germany
Gemeinschaftspraxis Dres. Schmitz, Steinmetz, Severin
Cologne, Germany
Klinikum der Universität zu Köln, Klinik I für Innere Medizin
Cologne, Germany
Krankenhaus Holweide
Cologne, Germany
St. Johannes Hospital Dortmund, Med. Klinik II
Dortmund, Germany
BAG Freiberg-Richter, Jacobasch, Wolf, Illmer
Dresden, Germany
Gemeinschaftspraxis Dres. Mohm, Prange-Krex
Dresden, Germany
Universitätsklinikum Erlangen, Med. Klinik 5
Erlangen, Germany
St.-Antonius-Hospital Eschweiler, Hämatologie und Onkologie
Eschweiler, Germany
Klinikum Esslingen, Klinik für Gastroenterologie, Onkologie und Innere Medizin
Esslingen am Neckar, Germany
Klinikum der J.W. Goethe-Universität Frankfurt, Hämatologie/Onkologie
Frankfurt, Germany
Krankenhaus Nordwest Frankfurt, II. Med. Klinik
Frankfurt, Germany
Klinikum Frankfurt (Oder), Abteilung f. Innere Medizin
Frankfurt (Oder), Germany
Praxis Dr. med. Reiber
Freiburg im Breisgau, Germany
Universitätsklinikum Freiburg, Innere Medizin I
Freiburg im Breisgau, Germany
Klinikum Fulda, Med. Klinik III
Fulda, Germany
St. Josef-Hospital Gelsenkirchen, Onkologie und Hämatologie
Gelsenkirchen, Germany
Praxis Dr. med. Schliesser
Giessen, Germany
Wilhelm-Anton-Hospital Goch, Innere Medizin
Goch, Germany
Onkologische Kooperation Harz, Onkologische Schwerpunktpraxis
Goslar, Germany
Universitätsmedizin Göttingen, Hämatologie und Onkologie
Göttingen, Germany
Universitätsmedizin Greifswald, Medizinische Universitätsklinik C, Hämatologie und Onkologie
Greifswald, Germany
Kreiskrankenhaus Gummersbach
Gummersbach, Germany
Klinikum Gütersloh
Gütersloh, Germany
Kath. Krankenhaus Hagen, St.-Marien-Hospital
Hagen, Germany
Gemeinschaftspraxis Rohrberg, Hurtz, Schmidt, Frank-Gleich
Halle, Germany
Asklepios Klinik St. Georg, Hämatologie/Onkologie
Hamburg, Germany
Hämatolog.-onkolog. Praxis Dres. Müller-Hagen, Bertram, Albertinen-Krankenhaus
Hamburg, Germany
Hämatologisch-onkologische Praxis Altona (HOPA)
Hamburg, Germany
Universitätsklinikum Hamburg-Eppendorf (UKE), II. Med. Klinik und Poliklinik, Onkologie und Hämatologie
Hamburg, Germany
Klinikum Hannover-Siloah, Klinik für Hämatologie
Hanover, Germany
Medizinische Hochschule Hannover (MHH), Zentrum für Innere Medizin, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
Hanover, Germany
Praxis MediProjekt
Hanover, Germany
Universitätsklinikum Heidelberg, Innere Medizin V
Heidelberg, Germany
Klinikum Kreis Herford, Med. Klinik II
Herford, Germany
Onkologische Schwerpunktpraxis Dres. Freier, Sievers
Hildesheim, Germany
St. Bernward Krankenhaus Hildesheim, Med. Klinik II
Hildesheim, Germany
KMT Klinik Idar-Oberstein
Idar-Oberstein, Germany
Universitätsklinikum Jena, Klinik für Innere Medizin II
Jena, Germany
Westpfalz-Klinikum, Klinik für Innere Medizin I
Kaiserslautern, 67655, Germany
Praxis Dres Hansen, Reeb
Kaiserslautern, Germany
St. Vincentius Kliniken Karlsruhe, Med. Klinik Abt. 2
Karlsruhe, Germany
Städtisches Klinikum Karlsruhe, II. Med. Klinik, Hämatologie/Onkologie/Infektionskrankheiten
Karlsruhe, Germany
GMP Dres Siehl, Söling
Kassel, Germany
Rotes Kreuz Krankenhaus Kassel, Klinik für Interdisziplinäre Onkologie
Kassel, Germany
Klinikum Kempten-Oberallgäu, Hämatologie, Onkologie und Palliativmedizin
Kempten, Germany
Gemeinschaftsklinikum Mittelrhein, Ev. Stift St. Martin, Innere Medizin
Koblenz, Germany
Gemeinschaftspraxis Dres. Neise, Lollert
Krefeld, Germany
Praxis Dr. Strauch
Kronach, Germany
Klinikum Landshut, Med. Klinik I
Landshut, Germany
Caritas Krankenhaus Lebach
Lebach, Germany
Onkologische Schwerpunktpraxis
Leer, Germany
Klinikum St. Georg Leipzig, Abteilung für internistische Onkologie/Hämatologie
Leipzig, Germany
Klinikum Lippe-Lemgo, Med. Klinik II
Lemgo, Germany
Onkologische Schwerpunktpraxis Lörrach
Loerrach, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Lübeck, Germany
Klinikum Magdeburg, Hämatologie/Onkologie
Magdeburg, Germany
Universitätsmedizin Mainz, III. Med. Klinik und Poliklinik
Mainz, Germany
Mannheimer Onkologie Praxis, Dres. Brust, Plöger, Schuster, Hensel
Mannheim, Germany
Universitätsklinikum Gießen und Marburg
Marburg, Germany
Johannes Wesling Klinikum, Klinik für Hämatologie, Onkologie und Palliativmedizin
Minden, Germany
Kliniken Maria-Hilf Mönchengladbach, Innere Medizin I
Mönchengladbach, Germany
Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin
Mutlangen, Germany
GMP Dres Schröder/Sieg
Mülheim, Germany
Klinikum Großhadern, Med. Klinik 3
München, Germany
Klinikum rechts der Isar der Technischen Universität München, III. Med.Klinik
München, Germany
Städtisches Klinikum München Harlaching
München, Germany
Praxis Dres. Schmidt, Fromm, Wiesmeier, Seufert, Klapthor, Zingerle
München Pasing, Germany
Universitätsklinikum Münster, Med. Klinik A
Münster, Germany
Onkologische Praxis Dr. Ladda
Neumarkt, Germany
Lukaskrankenhaus Neuss, Med. Klinik II
Neuss, Germany
Kreiskliniken Esslingen, Klinikum Kirchheim-Nürtingen, Hämatologie, Internist. Onkologie und Palliativmedizin
Nürtingen, Germany
Gemeinschaftspraxis Dres. Balló, Böck
Offenbach, Germany
Ortenau Klinikum Offenburg-Gegenbach, Medizinische Klinik II
Offenburg, Germany
Klinikum Oldenburg, Hämatologie/Onkologie
Oldenburg, Germany
Onkologische Schwerpunktpraxis Dr. Hübner
Oldenburg, Germany
Pius Hospital Oldenburg, Klinik für Strahlentherapie und Internistische Onkologie
Oldenburg, Germany
Onkologische Schwerpunktpraxis im MVZ 2 GmbH, Dr. H. Eimermacher
Olpe, Germany
Klinikum Osnabrück, Med. Klinik III
Osnabrück, Germany
Paracelsus Krankenhaus Ruit, Kreiskliniken Esslingen gGmbH, Zentrum für Allgemeine Innere Medizin
Ostfildern, Germany
Brüderkrankenhaus St. Josef Paderborn, Klinik für Hämatologie und Onkologie
Paderborn, Germany
Gemeinschaftspraxis Dres. Baake, Leonhardt, Moegling, am Regio Klinikum Pinneberg
Pinneberg, Germany
Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie und Palliativmedizin
Potsdam, Germany
Gemeinschaftspraxis Dres. Decker, Nonnenbroich, Herbrik-Zipp
Ravensburg, Germany
Prosper-Hospital Recklinghausen, Med. Klinik I
Recklinghausen, Germany
Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
Regensburg, Germany
Klinikum am Steinenberg, Kreiskliniken Reutlingen GmbH
Reutlingen, Germany
Elblandklinikum Riesa, Klinik für Innere Medizin II
Riesa, Germany
Klinikum Südstadt Rostock, Innere Medizin
Rostock, Germany
Universitätsklinikum Rostock, Abteilung Hämatologie/Onkologie, Klinik u. Poliklinik für Innere Medizin
Rostock, Germany
GMP Dres Jacobs, Daus, Schmits
Saarbrücken, Germany
ZAHO-Siegburg, Zentrum für ambulante Hämatologie und Onkologie Siegburg
Siegburg, Germany
Diakonie-Klinikum Stuttgart, Med. Klinik II
Stuttgart, Germany
Klinikum Traunstein, Hämatologie/Onkologie
Traunstein, Germany
Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I
Trier, Germany
Krankenhaus der Barmherzigen Brüder Trier, I. Med. Abteilung
Trier, Germany
Universitätsklinikum Tübingen, Medizinische Klinik und Poliklinik, Onkologie, Hämatologie, Immunologie und Rheumatologie
Tübingen, Germany
Universitätsklinikum Ulm, Innere Medizin III
Ulm, Germany
Katharinen Hospital Unna
Unna, Germany
Schwarzwald-Baar-Klinikum - Innere Medizin II
Villingen-Schwenningen, 78052, Germany
Praxis Onkologie Schwarzwald - Alb
Villingen-Schwenningen, Germany
Med. Versorgungszentrum Weiden, Abteilung für Onkologie
Weiden, Germany
Praxis Dres med. Perker, Sandherr
Weilheim, Germany
HSK Wiesbaden, Innere Medizin III
Wiesbaden, Germany
Helios Klinkum Wuppertal, Med. Klinik I
Wuppertal, Germany
Hämatologisch-Onkologische Praxis Würselen
Würselen, Germany
Related Publications (2)
Pfreundschuh, M., Christofyllakis, K., Altmann, B., Ziepert, M., Haenel, M., Viardot, A., Neubauer, A., Held, G., Truemper, L., Dreyling, M., Kanz, L., Hallek, M., Schmitz, N., Heintges, T., Kölbel, C., Buecker, A., Ruebe, C., Hellwig, D., Berdel, C., Poeschel, V., and Murawski, N. (2017) Radiotherapy to bulky disease PET-negative after immunochemotherapy in elderly DLBCL patients: Results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL>60 study of the DSHNHL. Hematological Oncology, 35( S2): 129- 130. doi: 10.1002/hon.2437_119.
BACKGROUNDKaddu-Mulindwa D, Altmann B, Held G, Angel S, Stilgenbauer S, Thurner L, Bewarder M, Schwier M, Pfreundschuh M, Loffler M, Menhart K, Grosse J, Ziepert M, Herrmann K, Duhrsen U, Huttmann A, Barbato F, Poeschel V, Hellwig D. FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials. Eur J Nucl Med Mol Imaging. 2021 Oct;48(11):3550-3559. doi: 10.1007/s00259-021-05348-6. Epub 2021 Apr 29.
PMID: 33928400DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lorenz Thurner, Professor
Saarland University, Saarland University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2011
First Posted
November 23, 2011
Study Start
November 1, 2011
Primary Completion
January 18, 2024
Study Completion
January 18, 2024
Last Updated
January 8, 2025
Record last verified: 2025-01