AGMT Mabtenance Investigator Meeting. 27. May 2011 Vienna / MuseumsQuartier

Transcription

1 AGMT Mabtenance Investigator Meeting 27. May 2011 Vienna / MuseumsQuartier

2 Chair and speakers: Univ. Prof. Dr. Richard Greil: President AGMT, Head of the IIIrd Medical Department, Private Medical UniversityHospital Salzburg, Austria MABTENANCE INVESTIGATOR MEETING Vienna Univ. Doz. Dr. Alexander Egle: IIIrd Medical Department, Private Medical UniversityHospital Salzburg, Austria Mag. Florian Miczka: Assign Data Management and Biostatistics GmbH, Innsbruck, Austria Mag. Martina Gantschacher: Director of the Department for Health Law & Science of the Sigmund Freud Private University Vienna, Austria Dr. Andy C.. Rawstron: Leeds Teaching Hospitals, Leeds, United Kingdom Mag. Gabriele Brachtl:: Labaratory of molecular cytology, Private Medical UniversityHospital Salzburg, Austria Prof. Dr. Michael Doubek, Interní hematoonkologická klinika LF MU a FN, Brno, Czech Republic Prof. Mikulas Hrubisko, FNsP sv. Cyrila a Metoda, Bratislava, Slovakia Prof. Georgi Mihaylov: National Specialized Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria Galafteon Oltean: County Emergency Clinical Hosptital Targu Mures, Romania 27 th May :30 17:30 (c) Hertha Hurnaus Barocke Suite A & B MuseumsQuartier/q21

3 AGENDA :30 Lunch Buffet Chair: Richard Greil (Austria), Michael Doubek (Czech Republic), Mikulas Hrubisko (Slovakia) Chair: Alexander Egle (Austria), Georgi Mihaylov (Bulgaria), Galafteon Oltean (Romania) 12:30 12:40 Welcome and Introduction Richard Greil (Salzburg, Austria) 12:40 13:10 Rational of the Study & Protocol Overview Alexander Egle (Salzburg, Austria) 13:10 13:30 Data Management Florian Miczka (Innsbruck, Austria) 13:30 14:00 Findings in Audits/ Quality in Studies Martina Gantschacher (Vienna, Austria) 14:00 14:30 Discussion 15:15 15:50 Assessing minimal residual disease (MRD) in CLL Andy Rawstron (Leeds, UK) 15:50 16:10 MRD evaluation : The Austrian experience Gabriele Brachtl (Salzburg/Austria) 16:10 16:30 MRD evaluation : The Czech experience Michael Doubek (Brno, Czech Republic) 16:30 17:25 Discussion 17:25 17:30 Closing Remarks Richard Greil (Salzburg, Austria) 14:30 15:15 Coffee Break & Meet the Experts 18:30 Dinner Glacis Beisl / MuseumsQuartier

4 AGMT Arbeitsgemeinschaft Medikamentöse Tumortherapie President: Univ. Prof. Dr. Richard Greil Head of the IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases Laboratory of Immunological and Molecular Cancer Research (LIMCR) Center for Clinical Cancer and Immunology Trials Private Medical University Hospital Salzburg

5 About AGMT AGMT (Arbeitsgemeinschaft medikamentöse Tumortherapie) is a nonprofit group of scientifically active clinicians and researchers in Haematology and Oncology. We have made it our goal, to carry out clinical studies to improve the results of treating patients suffering from malignant tumours and to facilitate investigations for better understanding of the results of the treatment. Since its establishment more than 1300 patients have been treated in more than 30 AGMT protocols in 35 hospitals in Austria.

6 Organisation Arbeitsgemeinschaft medikamentöse Tumortherapie President: Univ.Prof. Dr. Richard Greil Vicepresiden t: Univ.Prof. Dr. Josef Thaler, OA Dr. Otto Krieger AGMT non-profit GmbH Coordinating Investigator Director Univ.Prof. Dr. Richard Greil Commercial Director Josef Ragger, MBA (optional) Study Coordinator Clinical Trials Lead Manager Dr. Daniela Wolkersdorfer Clinical Projectmanager Mag. Alexandra Strasser Clinical Monitor Mag. Matthias Florian Clinical Projectmanager Mag. Josef Gassner-Uphues (part time) Clinical Monitor Dipl.Ing. (FH) Michaela Neuwirth Clinical Monitor Mag. Maria Bogensperger (part time) Clinical Monitor Barbara Meiniger Clinical Monitor Mag. Katrin Sinzinger (part time)

7 Geographic Coverage of AGMT - Cooperating Sites in Austria AGMT sites in Austria: 35 Bregenz Ried Wels Vöcklabruck AKH Linz BhS Linz Elisabethinen Steyr Waidhofen/T. Krems St. Pölten : AKH Wien Hanusch Rudolfsstiftung KFJ BB Wien WSP Soz.Med.Z. Ost Evang. KH Wien Dornbirn Innsbruck Kufstein Feldkirch Hohenems Hall Zams Salzburg Leoben Wr. Neustadt Fürstenfeld Klagenfurt St. Veit Villach Uniklinik Graz BB Graz

8 Jän.10 Mär.10 Mai.10 Jul.10 Sep.10 Nov.10 AGMT: Patient Numbers In patients were enrolled in AGMT protocols Number of Patients / year Recruitment 2010 patients patients planned

9 New AGMT Protocols protocols open for recruitment open for recruitment AGMT protocols were open for recruitment Hematooncology:10 protocols Solide tumors: 8 protocols protocols were submitted to the IRB and approved Hematooncology: 3 protocols Solide tumors: 9 protocols

10 AGMT PROTOCOLS 2010 open for recruitment 10 protocols overall 8 protocols overall In additional protocol was initiated (NHL) till now. In additional protocols were initiated (3 esophag./gastric/crc, 1 Mamma CA, 1 other- HNO)

11 European Cooperations: AGMT in Europe DHSG Deutsche Hodgkin Studiengruppe AIO (Arbeitsgemeinschaft internistische Onkologie) StiL (Studiengruppe indolente Lymphome) DSHNHL (Deutsche Studiengruppe Hochmaligne NHL) EWALL (European Working Group for Adult Acute LymphoblasticLleucemia) GELARC (Groupe d Etude des Lymphomes de l Adulte - Recherche Clinique) Nordic Lymphoma Group SAKK (Swiss Group for Clinical Cancer Research ) Studiengruppe Prof. VanCutsem Belgien Mabtenance International AGMT trial (started in 2010): Cooperations with Czech Republic, Slovakia, Romania and Bulgaria

12 EUROPEAN COOPERATIONS OF AGMT AIO (Arbeitsgemeinschaft internistische Onkologie) Czech Lymphoma Study Group DHSG Deutsche Hodgkin Studiengruppe DSHNHL (Deutsche Studiengruppe Hochmaligne NHL) EWALL (European Working Group for Adult Acute LymphoblasticLleucemia) GELARC (Groupe d Etude des Lymphomes de l Adulte - Recherche Clinique) Nordic Lymphoma Group SAKK (Swiss Group for Clinical Cancer Research ) StiL (Studiengruppe indolente Lymphome) Studiengruppe Prof. VanCutsem Belgium Sites in Slovakia, Romania and Bulgaria GELARC VanCutsem StiL DSHNHL DHSG EWALL AIO Nordic Lymphoma Group Czech Lymphoma Study Group Slowakei AGMT Bulgaria SAKK Romania In red: Cooperation with study groups which started in 2010

13 HEMATOONCOLOGIC TRIALS TITLE STATUS PHASE INCLUSION TREATMENT HD HD 13 Active (not recruiting) HD 14 HD 15 HD 16 Active (not recruiting) Active (not recruiting) Submission ongoing HD 18 Active (36 patients) III HD early stage 2x ABVD + 30 Gy IF-RT vs. 2x AVD + 30 Gy IF-RT III HD intermediate stage 2 x BEACOPP + 2x ABVD + IF-RT vs. 4 x ABVD + IF-RT III HD advanced stage 8x BEACOPPesk vs 6x BEACOPPesk vs 8x BEACOPP14 + IF-RT (PET pos) III HD early stage Stratification acc. to FDG-PET: 30Gy IF-RT vs observation III HD advanced stage Stratification acc. to FDG-PET: BEACOPP +/- Rituximab CLL FLUSALEM closed II CLL 2nd / 3rd line F + Alemtuzumab Chairos Active (not recruiting) II CLL ist line 3 cycles FCR > 3 cycles FR > 2 years of R maintenance BendAlem active I/II Relapsed CLL, 2nd line Bendamustin + Alemtuzumab RevliRit Active (not recruiting) Mabtenance Active (30 patients) i/ii CLL 1st line FR Lenalidomid, maintenance: R, L III CLL, Maintenence after R based induction Rituximab vs. observation

14 HEMATOONCOLOGIC TRIALS cont NHL TITLE STATUS PHASE INCLUSION TREATMENT NHL8, 9,10,12 closed NHL 11 closed II Mantle cell lymphoma, 1 st line NHL 13 NHL 14 NHL /A active (not recruiting) active (not recruiting) active (47 patients) III II II/III aggressive B-Zell Lymphoma aggressive B-Zell Lymphoma Progredient follicular lymphona and other low grade NHL and mantle cell lymphoma R-CHOP-Thal, followed by Thal maintenance Rituximab maintenance vs observation R-CHOP vs R-COMP Bendamustin Rituximab Ind. Maintanance: 2 vs 4 years R (foll. lymphoma) or 2 years R vs observation REMARC just initiated III DLBCL, age 60 to 80 After response to R CHOP randomisation ro Lealidomid maintenance or placebo for 24 months

15 HEMATOONCOLOGIC TRIALS con t TITLE STATUS PHASE INCLUSION TREATMENT PTCL PTCL 1 active (4 patients) ACT 1 active (2 patients) ACT 2 active (2 patients) MALT MALT active (not recruiting) MDS Vidaza Registry active (199 patients) CMML CMML active (4 patients) I/II PTCL, 2nd line Lenalidomid + Vorinostat + DM II PTCL 1st line, age < 60 PTCL 1st line, age > 60 Advanced MALT Lymphoma, 2nd line Registry MDS, CMML, AML Vidaza Alemtuzumab in combination with CHOP versus CHOP alone and consolidated by autologous stem cell transplant Alemtuzumab in combination with CHOP versus CHOP alone Rituximab + 2CdA II CMML Lenalidomid dose finding (starting dose 20 mg)

16 Clinical trials of the AGMT in CLL

17 FLUSALEM: Design relapsed/refractory continous alemtuzumab 30mg sc.3 times weekly during all cycles 4 cycles fludarabine 40mg/m² d1-3; q 29d Staging 1 Staging 2

18 FLUSALEM: Publications Egle, A.; Melchardt, T.; Pleyer, L.; Tinhofer, I.; Lang, A., Keil, F.; Thaler, J.; Fridrik, M., Gunsilius, E.; Greil, R. Final results of oral fludarabine with concomitant subcutaneous alemtuzumab in relapsed/refractory B-chronic lymphocytic leukaemia (B- CLL): The FLUSALEM study EHA 2009 Haematologica-the Hematology Journal 2009;94:140. Egle, A, Tinhofer, I, Russ, G, Rass, C, Greil, R Planned first safety and efficacy analysis of oral fludarabine combined with subcutaneous alemtuzumab in 2(nd) line therapy of B-chronic lymphocytic leukaemia (B-CLL): The FLUSALEM study. 48th Annual Meeting of the American-Society-of-Hematology BLOOD 108, 4990, 2006

19 CHAIROS (CLL4): Design 1st line

20 CHAIROS (CLL4): Publications Egle A, Weiss L, Melchardt T, Gunsilius E, Petzer AL, Fridrik M, Lang A, Krieger O, Thaler J, Greil R. Final Analysis of Induction Treatment with Fludarabine, Cyclophosphamide Plus Rituximab (FCR) Followed by Fludarabine Plus Rituximab (FR) and Remission Maintenance Therapy with Rituximab In Previously Untreated B-Chronic Lymphocytic Leukemia (B-CLL): The Chairos AGMT CLL4/Roche ML18434 Study. Blood 116: 1380, Egle, A, Weiss, L, Gassner, F, Russ, G, Pleyer, L, Gunsilius, E, Tinhofer, I, Thaler, J, Petzer, AL, Greil, R Minimal Residual Disease (MRD) and T/NK Cell Dynamics during Fludarabine, Cyclophosphamide Plus Rituximab (FCR) Followed by Fludarabine Plus Rituximab (FR) and Remission Maintenance Therapy with Rituximab in Previously Untreated B- Chronic Lymphocytic Leukemia (B-CLL): Riskfactor Stratification in the Chairos Study. 50th Annual Meeting of the American- Society-of-Hematology Blood 112, 1089, 2008

21 CHAIROS (CLL4): Publications Egle, A, Weiss, L, Russ, G, Thoedtmann, R, Pleyer, L, Gastl, G, Thaler, J, Petzer, A, Tinhofer, I, Greil, R Planned first efficacy and safety analysis of de-intensified induction with fludarabine, cyclophosphamide plus rituximab (FCR) followed by fludarabine plus rituximab (FR) and remission maintenance therapy with rituximab in previously untreated B-chronic lymphocytic leukaemia (B-CLL): The chairos study 49th Annual Meeting of the American-Society-of-Hematology BLOOD 110, 2045, 2007

22 RevliRit (CLL5): Design D1 wk 5 wk 9 wk 13 wk 17 wk 21 wk 24 wk29 wk 33 wk 37 wk 41 wk 45 wk 49 wk53 Fludarabin Rituximab Lenalidomide MRD/Staging Induction: INDUCTION: 4-weekly cycles MAINTENANCE: Rituximab in 8-weekly cycles, Lenalidomide in 4-weekly cycles; max. 6 months Fludarabine 25 mg/m2 iv d1-3 or 40mg/m2 po d1-3 repeat every 28 days Rituximab 375mg/m2 iv day 4 on cycle 1 repeat every 28 days 500mg/m2 iv day 1 on cycles 2-6 Lenalidomide day 8-21 of cycle 1 day 1-21 of cycles 2-5 Maintenance: Rituximab 375mg/m2 iv 2/4/6 months after end of phase I Lenalidomide day 1-28 of 28 day cycles for 6 months at the maximal dose level reached in phase I

23 RevliRit (CLL5): Publications Egle A, Steurer M, Melchardt T, Stoll M, Greil R. The Revlirit Cll5 Agmt Study - A Phase I/Ii Trial Combining Fludarabine/Rituximab with Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (Cll): Results of A Planned Interim Analysis. Blood 2009;114:

24 Bendalem (CLL6): Design Relapsed/refractory Ind. Maintenance Follow Up Bendamustin wk-1 D1 wk 5 wk 9 wk 13 wk 17 M6 M10 M16 Alemtuzumab MRD/Staging d1+d2 Weekly on days 1, 3, 5 Induction: Alemtuzumab mg s.c. on days -3, -2, -1 Maintenance: Bendamustine 70 mg/m2 iv d1 + d2 repeat every 28 days for 4 cycles Alemtuzumab 30 mg s.c. 3x/week (days 1, 3, 5) in parallel with chemotherapy for max.16 weeks

25 Bendalem (CLL6): Publications Egle A, Melchardt T, Weiss L, Steurer M, Greil R. The BENDALEM CLL 6 AGMT Study Bendamustine Combined with Alemtuzumab In Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL): Results of a Planned Interim Analysis. Blood 116: 4633, 2010.

26 Rituximab containing induction treatment Response evaluation Partial response, complete response Stable disease, disease progression MABTENANCE CLL 8 / A International, Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment versus Observation alone in Patients with Chronic Lymphocytic Leukemia NOT ELIGIBLE REGISTRATION AND STUDY START ENTER SCREENING RANDOMISATION enter screening minimum 3 months, maximum 6 months after last induction treatment administration Observation for 24 months 8 x Rituximab 375mg/m² every 3 months for 24 months 2 years follow-up

27 Mabtenance: Sites in Austria Feldkirch Kufstein Innsbruck (6 patients) Hall AKH Linz Wels (1 patient) (1patient) Salzburg (8 Patients) Steyr (3 patients) Krems (3 patients) AKH Wien Hanusch Wien 11 Sites in Austria: 22 patients have been enrolled in Austria.

28 International Sites

29 Mabtenance: Start international Slovakia Czech Republic Bulgaria Romania Q Q Q Sites Patients Czech Republic 5 Slovakia 7 8 Bulgaria 4 Romania 4

30 Mabtenance sites: initiated Number Site Meeting participants Initiation Patients A 01 Salzburg Prof. Dr. Richard Greil Doz. Dr. Alexander Egle Mag. Michaela Schachner A 02 Innsbruck Prof. Michael Steurer A 03 Kufstein A 04 Hall in Tirol Dr. Horst Öxle A 05 AKH Wien Prof. Dr. Ulrich Jäger A 07 AKH Linz Doz. Dr. Michael Fridrik A 08 Wels A 09 Steyr A 10 Krems Prof. Martin Pecherstorfer Gabriele Schmoranzer A 11 Feldkirch SL 01 Martin Dr. Daniela Kotulicova SL 02 Bratislava 1 Dr. Miriam Ladicka Dr. Daniela Svetlovská SL 03 Bratislava 2 Dr. Daniela Svetlovská SL 04 Banska Bystrica SL 05 Bratislava 3 Prof. Mikulas Hrubisco SL 06 Presov pending SL 07 Kosice pending

31 Mabtenance Sites: not yet initiated Number Site Meeting participants CZ 1 Brno Prof. Michael Doubek CZ 2 Hradec Králové Dr. Martin Simkovic Dr. Vladimir Gerov CZ 3 Olomouc Dr. Branimir Spasov CZ 4 Praha 1 Dr. Martin Spacek CZ 5 Praha 2 Dr. Petra Obrtlikova Dr. Peter Turcsanyi BUL 1 Sofia Prof. Dr. Georgi Mihaylov Dr. Branimir Spasov BUL 2 Varna Prof. Dr. Liana Gercheva Dr. Vladimit Gerov BUL 3 Plovdiv Vasko Graklanov Dzhahide Faris Enim BUL 4 Sofia Prof. Dr. Julian Raynov Dr. Ivan Damyanov RO 1 Bucharest Dr. Anca Ciobanu Livia Pirvan RO 2 Târgu Mureș Prof. Dr. Galafteon Oltean Emilia Bonita RO 3 Timişoara Dr. Florica Ghilezan Dr. Despina Calamar Popovici RO 4 Iaşi Dr. Cristina Burcoveanu Florina Farca

32 MABTENANCE: Recruitment 256 patients planned, recruitment will be prolonged till end of Q Q 2 Q3 Q4 Q1 Q patients Q planned Q Q Q Q Q4 2012

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