CLLM1-PROTOCOL OF THE GERMAN CLL-STUDY GROUP (GCLLSG)
Screening supported by a central review allows a precise selection of the population for maintenance therapy within the
CLLM1 trial of the German CLL Study Group
1Anne Westermann, DCLLSG, Uniklinik Köln, 22.02.2014 DKK
Personalized treatment plan tailored to patients needs and diagnosis.Approach: individualized CLL therapy
Staging Lymphocyte doubling time Response to treatment
Physical fitnessGo goslow go No go
Molecular cytogenetics17p-Deletion, TP53
Mutation, ….
MRDIntensify therapy if MRD+Maintenance therapy?
Patient-specific treatmentcomorbidities, renal function…
+CLL-specific treatmentMolecular cytogenetics, Lymphocyte doubling time, Serum thymindine kinase…
RATIONALE OF CLLM1
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Patients with high risk of early PD after Firstline have
short survival
no standard treatment options
few patients are eligible for stem cell transplantion
Why Lenalidomide?
effective and approved for treatment of relapsed and refractory multiple myelomaensures recovery of T-cell defects
direct CD8+ T-cell killing of B-CLL cells
High MRD level≥10-2
Median MRD level ≥ 10-4 -<10-2
combined with at least one of the following
del(17p) TP53 mutation unmutated IGHV-
status
DEFINITION OF HIGH RISK
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or
Physically fit and previously untreated patients with treatment requiring disease CLLM1-STUDY DESIGN
Firstline investigator‘s choice (FCR, BR, FR (FC)
Treatment up to PD
700screening patients
High Risk
High Risk2: 1
Rando
200randomized patients
placeboL‐maintenance
Complete or incomplete local
results of TP53, 17p, IGHV
CLLM1 TRIAL
•
Up to 6 months prior to Firstline therapy
4‐6 months firstline therapy
2‐5 months after end of last cycle
Risk Assessment:Patients with low riskPatients with high risk
Central lab results of
TP53, 17p, IGHV
Central lab results of
TP53, 17p, IGHV
Mandatory MRD‐Analysis in Kiel
Risk assessments performed within 8 to 13 months
Firstline‐Therapy
MEDICAL REVIEW
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Patient data are checked by GCLLSG Physicians
Fit patients: CIRS<6
Response to Firstline
Renal function: Crea-clearance > 60ml/min
Exclusion of active Infection/Hematoxicity
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PATIENTS DROP OUT/ LOW RISK
32Drop outs
442Registered patients
162Pts screened after firstline
34Pts randomized
Firstline Therapy
69Drop outs
123Pts with low risk
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REASONS FOR DROP OUT
1 patient’s Decision
2 other disease
3 no adequate firstline therapy
4 treatment related reasons
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REASONS FOR PATIENT‘S WITHDRAWAL
SURVEY DECEMBER 2013
1 tired of treatment
2 afraid of lenalidomide side effects
3 concerned of frequent visits
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CONCLUSION
Maintenance therapy after a careful selection of a subgroup with high risk is feasible if
Patients and doctors are convinced of the study drug and the benefits of maintenance therapy
Thank you!Prof. Martin Dreyling, München; Dr. Ingo Ringshausen, München; Dr. Sebastian Böttcher, Kiel; Dr. Cordelia Steinbrecher, Erfurt; Dr. Jan Dürig, Essen; Prof. Thorsten Zenz, Heidelberg; Prof. Michael Pfreundschuh, Homburg/Saar; Dr. Barbara Eichhorst, Köln; Dr. Florian Heidel, Magdeburg; Dr. Martin R. Müller, Tübingen; Dr. Peter Staib, Eschweiler; Dr. Jochen Pfirstinger, Regensburg; Prof. Lothar Bergmann, Frankfurt; Dr. Matthias Port, Hannover; Prof. Christian Andreas Schmidt, Greifswald; Prof. Stephan Stilgenbauer, Ulm; Dr. Kordelia zur Hausen, Aachen; Dr. Karin Heinisch, Lemgo; Prof. Clemens-M. Wendtner, München; Dr. Otto Prümmer, Kempten; Dr. Peter Reimer, Essen; Dr. Beate Schultheis, Herne; Prof. Matthias Zeis, Hamburg; Dr. Elisabeth Lange, Hamm; Dr. Heinz A. Dürk, Hamm; Dr. Eva Roemer, Idar-Oberstein; Dr. Stefan Mahlmann, Kaiserslautern; Dr. Frank Heits, Rotenburg; Dr. Stefan Kremers, Lebach; Dr. Alexander Wacker, Reutlingen; Dr. Cornelia Winkelmann, Lutherstadt-Wittenberg; Dr. Marcus Hentrich, München; Prof. Holger Hebart, Mutlangen; Prof. Georg Maschmeyer, Potsdam; Dr. Heribert Stauder, Regensburg; Dr. Thomas Geer, Schwäbisch Hall; Dr. Rolf Mahlberg, Trier; Prof. Doris Kraemer, Oldenburg; Dr. Christoph Diekmann, Bremen; Prof. Claudio Denzlinger, Stuttgart; Dr. Ullrich Graeven,Mönchengladbach; Dr. Michael Flaßhove, Düren; Prof. Heinz-Gert Höffkes, Fulda; Prof. Bernd Hertenstein, Bremen; Prof. Martin Bentz, Karlsruhe; Dr. Walter Lindemann, Hagen; Dr. Barbara Günther, Düsseldorf; Dr. Henry Simon, Ostfildern; Dr. Ludwig Fischer von Weikersthal, Amberg; Dr. Tobias Gaska, Paderborn; Dr. Alexander Kröber, Regensburg; Prof. Markus Bangerter, Augsburg; Dr. Michael Josef Eckart, Erlangen; Dr. Alexander Schmittel, Berlin; Dr. Philipp Kiewe, Berlin; Dr. Ulrich von Grünhagen, Cottbus; Dr. Thomas Illmer, Dresden; Dr. Robert Rohrberg, Halle; Dr. Ursula Vehling-Kaiser, Landshut; Doris Fleckenstein, München; Dr. Burkhard Schmidt, München; Dr. Rudolf Schmits, Saarbrücken; Dr. Martina Stauch, Kronach; Dr. Sebastian Müller, Ansbach; Dr. Ali Aldaoud, Leipzig; Dr. Holger Nückel, Bochum; Dr. Ulrike Söling, Kassel; Dr. Ulla von Verschuer, Essen; Dr. Hartmut Linde, Potsdam; Dr. Stefan Fronhoffs, Siegburg; Dr. Michael Sandherr, Weilheim; Dr. Daniel Reschke, Oldenburg; Dr. Thomas Decker, Ravensburg; Dr. Jörg Thomalla, Koblenz; Dr. Tobias Reiber, Freiburg; Dr. Christina Balser, Marburg; Dr. Rudolf Schlag, Würzburg; Dr. Ekkehart Ladda, Neumarkt; Prof. Stephan Schmitz, Köln; Dr. Claus-Christoph Steffens, Stade; Dr. Herbert Lebahn, Berlin; Dr. Kathleen Jentsch-Ullrich, Magdeburg; Dr. Hans-Peter Böck, Offenbach; Prof. Michael Koenigsmann, Hannover; Dr. Robert Eckert, Wendlingen; Dr. Oswald Burkhard, Worms; Dr. Richard Hansen, Kaiserslautern; Dr. Sigrun Müller-Hagen, Hamburg; Dr. Georg Schliesser, Gießen; Dr. Volkmar Böhme, Hamburg; Dr. Helmut Forstbauer, Troisdorf; Dr. Martin Teich, Chemnitz; Dr. Georg Köchling, VS-Villingen; Dr. Volker Lakner, Rostock; Steffen Dörfel, Dresden; Dr. Martine Klausmann, Aschaffenburg; Dr. André Lollert, Krefeld; Prof. Wolfgang Knauf, Frankfurt/Main; Prof. Manfred Hensel, Mannheim; Dr. Stefan Fuxius, Heidelberg; Dr. Peter Schmidt, Neunkirchen; Dr. Lothar Müller, Leer; Jörg Seraphin, Northeim; Dr. Lars Scheuer, Speyer; Dr. Roland Repp, Bamberg; Dr. Felix Marquard, Celle; Dr. Gerold Baake, Pinneberg; Dr. Michael Rieger, Darmstadt; Dr. Holger Schulz, Frechen; Dr. H.W. Tessen, Goslar; Dr. Godehard Obst, Burgwedel; Prof. Walter Verbeek, Bonn; Dr. Hans Reinel, Schweinfurt; Dr. Johannes Mohm, Dresden; Dr. Hanns Detlev Harich, Hof; Prof. Kai Uwe Chow, Frankfurt am Main; Dr. Ali-Nuri Hünerlitürkoglu, Neuss; Dr. Marcel Reiser, Köln; Prof. Michael Kiehl, Frankfurt an der Oder; Dr. Ulrike Enser-Weis, Bochum; Dr. Ute Kreiter, Mainz; Dr. Heike Steiniger, Oberhausen; Dr. Jan Schröder, Mülheim an der Ruhr; Dr. Uwe Sauer, Nordhorn; Dieter Mainka, Köln; Till-Oliver Emde, Recklinghausen; Dr. Matthias Egger, Lahr; Dr. Klaus Stengele, Singen; Prof. Jens Atzpodien, Georgsmarienhütte; Thomas Boldt, Freiberg