ALL-RELAPSE GROUP Päivi Lähteenmäki on behalf of the group

Transcription

1 ALL-RELAPSE GROUP Päivi Lähteenmäki on behalf of the group

2 Meeting in Bergen and 2 telephone meetings (Sept, Oct) IntReALL-group in Lissabon (September, Thomas F) IntReALL SR : Denmark has registered its first patient (paperwork as Marvin not in place yet). Copies of registrations should be sent to the Nordic study center in Stockholm (fax nr , dr Mats Heyman. E- mail adress support-cceg@kbh.ki.se) Norway and Finland have had a phone initiation meeting with Charite, and are ready to include patients. Sweden has some legal issues to solve until ready. These are insurance issues for those receiving Epratuzumab. There are also problems with the cosponsor delegation contract, with the two juridical bodies in Stholm, KI and KS.

3 All PIs and group members agree on that a common Marvin training should be set up by Mats, at a time when the system is running. SCT and cooperation SCTgroup: Jochen Büchner will present outlines of the IntReALL study for the Nordic SCTgroup at their next meeting. All patients should be eligible for the actual randomised study on conditioning +/- TBI. Resistant disease BFM group meeting in Stockholm 5-6 Feb 2015 Next Relapse WG meeting: Nov 24

4 IntReALL HR 2010 International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A randomized Phase II Study Conducted by the Resistant Disease Committee of the International BFM Study Group Protocol Version 1.6, Date Eudra-CT Number:

5 Objectives Primary: Improvement of complete remission rates in HR relapsed ALL patients Secondary: Improvement of EFS and OS rates Improvement of MRD reduction after induction with versus without bortezomib Toxicity of induction with versus without bortezomib Efficacy of consolidation elements to reduce MRD load until allo-hsct

6 Definition of high risk group: any T-cell bone marrow (BM) relapse any very early (<18 months from diagnosis) isolated or combined BM and/or extramedullary (EM) relapse early (up to 6 months from the end of therapy) isolated B-cell precursor (BCP) BM relapse

7 It contains the following treatment arms: induction: 1. prospective, randomized, open label phase II trial comparing arm A (modified ALL R3) versus arm B (modified ALL R3 + bortezomib). 2. single arm phase II trial (modified ALL R3 + bortezomib) compared with historical controls in groups opting out of randomization post-induction (HC1 (modified AIEOP-BFM ALL 2009 HR1), HC2 (modified HR3)): single arm observational trial a third post-induction chemotherapy block HC3(modified HR2) may optionally be given within the IntReALL HR 2010 trial or used as standard comparator for an investigational window trial

8 all patients in CR2 will be subjected to allogeneic HSCT termination of the trial after completion of the 2 nd or 3 rd consolidation block before investigational widow trial and/or allogeneic HSCT. Follow-up will be done until reaching secondary EFS / OS endpoints. For T-cell BM relapse, the patients might be withdrawed from the current study before its completion in the case of a specific international investigator sponsored trial intitiation in the forthcoming years

9 HR week Arm HR-A R Arm HR-B HIA (R3Mitox) HIB (R3Mitox+B) HC1 (mhr1) HC2 (mhr3) HC3 (mhr2) Invest. Window Termination of IntReALL Trial SCT BM/MRD week Arrow down ( ), bone marrow puncture with CR/MRD assessment; B, Bortezomib; HIA/B: HR induction arm A/B; HC1-3: HR consolidation 1-3; HR: high risk group; Invest., investigational; mhr1-3, modified BFM HR1-3 courses; MRD: minimal residual disease; R: randomization; R3Mitox, ALL-R3 backbone with mitoxantrone; SCT: stem-cell transplantation

10 Induction therapy: Course HIA or HIB

11 Course HC1 Agent Dosage Application Week 5 Week 6 Week 7 Dexamethasone 10 mg/m²/d PO Vincristine ARA-C Methotrexate Cyclophosphamide 1,5 mg/m²/d 2 g/m² 1g/m² 200 mg/m² PO IV IV 36 h IV 1 h PEG-Asparaginase 1000 U/m² IV 2 h / IM Methotrexate Cytarabine Age dep. Age dep. IT IT Prednisolone Age dep. IT Day

12 Course HC2 Agent Dosage Application Week 8 Week 9 Week 10 Dexamethasone 10 mg/m²/d PO ARA-C Etoposide 2 g/m² 100 mg/m² IV IV 1 h PEG-Asparaginase 1000 U/m² IV 2 h / IM Methotrexate Cytarabine Age dep. Age dep. IT IT Prednisolone Age dep. IT Day

13 Course HC3 Agent Dosage Application Week 11 Week 12 Week 13 Dexamethasone 10 mg/m²/d PO Vincristine Daunorubicin Methotrexate Ifosfamide 1,5 mg/m²/d 30 mg/m² 1g/m² 800 mg/m² PO IV 24h IV 36 h IV 1 h PEG-Asparaginase 1000 U/m² IV 2 h / IM Methotrexate Cytarabine Age dep. Age dep. IT IT Prednisolone Age dep. IT Day

14 Expected duration of the trial Start of the IntReALL HR 2010 trial End of patient recruitment (3 years) End of the trial (3 years follow-up for each patient) last patient out Further follow-up will be done by national cancer registries.

15 Budget for the HR protcol: For most NOPHO countries, the expenses budgeted were only for the SR protocol. The proportion between SR and HR patients should be calculated from NOPHO data. Stefan S. will negotiate with Arendt S/Berlin. Bortezomib and study centres: we suppose this is not a company driven study, but an Academic one. Demands such as those of AMGEN below are probably not to be expected. UK will participate in the Bortexomib part of the HR study. AMGEN and study centres: It is unclear what demands the sponsor poses for to participate in the Blinatumomab part of the HR protocol. Ideally, they want one center only In NOPHO. Maybe they can accept one center per country? In Norway, a decision has been made not to send patients abroad for BiTE treatment. And Amgen has not accepted Oslo as the only Nordic center for the study due to the low number of expected patients annually. There has been no Amgen proposals to our PIs the last month.