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…

OUTCOME CLL8 TRIAL

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PFS according to 17p PFS according to TP 53

OUTCOME CLL8 TRIAL

4

PFS according to IGHV PFS according to MRD

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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REASONS FOR PATIENT‘S WITHDRAWAL

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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