Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT
- Conditions
- Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT06061094
- Lead Sponsor
- Goethe University
- Brief Summary
The current Standard of Care (SoC) in younger patients with Ph+ ALL is Imatinib in combination with low-dose chemotherapy, change of TKI in case of persistent MRD above 10-3 after consolidation I and indication for stem cell transplantation.
The EVOLVE trial aims to answer three questions challenging the current SoC:
Use of Ponatinib compared to Imatinib both in combination with low-dose chemotherapy and consolidation I (randomization I).
In MRD good responders: Omit end of therapy in primary care and indication for SCT but continue therapy with TKI, chemotherapy and Blinatumomab as additional antileukemic compound (randomization II).
In MRD poor responders: Omit indication for TKI change but give instead Blinatumomab followed by end of therapy in primary care and indication for SCT (non-randomized).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- Male or female patients >= 18 years, <=65 years
- Philadelphia chromosome or BCR-ABL1 positive ALL
- Not previously treated except with corticosteroids ≤ 7 days, standard GMALL prephase with dexamethasone and cyclophosphamide including intrathecal therapy, hydroxyurea, a single dose vincristine or other cytostatic drugs and start of standard induction for Ph-positive ALL (1 dose vincristine, 1 dose of Rituximab, 2 doses dexamethasone and up to 5 days Imatinib)
- ECOG performance status ≤2
- Signed written inform consent
- Molecular evaluation for BCR-ABL1 performed
- Negative pregnancy test in women of childbearing potential
- Woman of childbearing potential willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment (Pearl-Index <1%). Male who has a female partner of childbearing potential willing to use 2 highly effective forms of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment (Pearl-Index <1%).
- Normal serum levels > LLN (lower limit of normal) of potassium and magnesium, or corrected to within normal limits with supplements, prior to the first dose of study medication
- Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis
- Normal QTcF interval ≤450 ms for males and ≤470 ms for females
- Signed and dated written informed consent is available
- Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)
- History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of protocol-specified therapy with defined exceptions
- Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab
- Patient previously treated with tyrosine kinase inhibitors
- Nursing women
- Known impaired cardiac function, including any of the following: as detailed in protocol
- Symptomatic peripheral vascular disease
- Any history of ischemic stroke or transient ischemic attacks (TIAs)
- Uncontrolled hypertriglyceridaemia
- History or presence of clinically relevant CNS pathology as detailed in protocol
- History or active relevant autoimmune disease
- Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C
- History of pancreatitis within 6 months previous to start of treatment within the trial
- Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
- Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
- Total bilirubin > 1.5-fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
- Concurrent severe diseases which exclude the administration of therapy e.g. severe, uncontrolled acute or chronic infections
- Inability to understand and/or unwillingness to sign a written informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and Blinatumomab Imatinib Molecular CR: No end of therapy with indication for SCT but and continuation with Imatinib/Ponatinib (per Randomization I), chemotherapy and Blinatumomab (Experimental Arm of Randomization II) C: Molecular CR: End of therapy with indication for SCT Indication for stem cell transplantation Molecular CR: End of therapy with indication for SCT (Standard Arm of Randomization II) A: Imatinib + low dose chemotherapy Imatinib Imatinib 600mg QD + low dose chemotherapy induction and consolidation I (Standard Arm of Randomization I) E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina Indication for stem cell transplantation Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm) B: Ponatinib + low dose chemotherapy Ponatinib Ponatinib 45mg QD (reduction to 30mg QD after Induction) + low dose chemotherapy induction and consolidation I (Experimental Arm of Randomization I) D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and Blinatumomab Ponatinib Molecular CR: No end of therapy with indication for SCT but and continuation with Imatinib/Ponatinib (per Randomization I), chemotherapy and Blinatumomab (Experimental Arm of Randomization II) D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and Blinatumomab Blinatumomab Molecular CR: No end of therapy with indication for SCT but and continuation with Imatinib/Ponatinib (per Randomization I), chemotherapy and Blinatumomab (Experimental Arm of Randomization II) E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina Ponatinib Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm) E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina Imatinib Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm) E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina Blinatumomab Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm)
- Primary Outcome Measures
Name Time Method OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care) up to 4 years from randomization I Probability of overall survival up to 4 years from randomization I in patients with mo-lecular remission after consolidation 1 comparing a combination treatment of TKI, Blina-tumomab and chemotherapy versus EOT with indication for SCT
- Secondary Outcome Measures
Name Time Method Rate of molecular complete remission at week 11 after consolidation week 11 after consolidation Rate of molecular complete remission at week 11 after consolidation with chemotherapy in combination with Ponatinb versus Imatinib
Trial Locations
- Locations (85)
Evangelische Kliniken Bonn
🇩🇪Bonn, Germany
Klinikum Bayreuth
🇩🇪Bayreuth, Germany
Vivantes Klinikum am Urban
🇩🇪Berlin, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Helios Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Uniklinik RWTH Aachen
🇩🇪Aachen, Germany
Klinikum Aschaffenburg
🇩🇪Aschaffenburg, Germany
Klinikum Augsburg
🇩🇪Augsburg, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Vivantes Klinikum Neukölln
🇩🇪Berlin, Germany
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Charite Berlin Virchow Klinikum
🇩🇪Berlin, Germany
Evangelisches Krankenhaus Bielefeld
🇩🇪Bielefeld, Germany
UK Knappschaftskrankenhaus Bochum
🇩🇪Bochum, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Städtisches Klinikum Braunschweig
🇩🇪Braunschweig, Germany
Klinikum Bremen-Mitte
🇩🇪Bremen, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
Klinikum Darmstadt
🇩🇪Darmstadt, Germany
Städtisches Klinikum Dessau
🇩🇪Dessau-Roßlau, Germany
Klinikum Dortmund
🇩🇪Dortmund, Germany
St. Johannes Hospital Dortmund
🇩🇪Dortmund, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Helios Klinikum Duisburg
🇩🇪Duisburg, Germany
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
St.-Antonius-Hospital
🇩🇪Eschweiler, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Evangelisches Krankenhaus Essen-Werden
🇩🇪Essen, Germany
Department of Medicine, Hematology and Oncology, Goethe University Hospital Frankfurt
🇩🇪Frankfurt, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Niels-Stensen-Kliniken Georgsmarienhütte
🇩🇪Georgsmarienhütte, Germany
Wilhelm-Anton-Hospital
🇩🇪Goch, Germany
Universitätsmedizin Greifswald
🇩🇪Greifswald, Germany
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Klinikum Gütersloh
🇩🇪Gütersloh, Germany
Katholisches Krankenhaus Hagen
🇩🇪Hagen, Germany
Universitätsklinikum Halle
🇩🇪Halle, Germany
Asklepios Klinik St. Georg Hamburg
🇩🇪Hamburg, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Marien Hospital Herne
🇩🇪Herne, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Germany
Klinikum Idar-Oberstein
🇩🇪Idar-Oberstein, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Städtisches Klinikum Karlsruhe
🇩🇪Karlsruhe, Germany
St. Vincentius-Kliniken Karlsruhe
🇩🇪Karlsruhe, Germany
Klinikum Kassel
🇩🇪Kassel, Germany
Universitätsklinikum Kiel
🇩🇪Kiel, Germany
Gemeinschaftsklinikum Mittelrhein
🇩🇪Koblenz, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Märkische Kliniken Lüdenscheid
🇩🇪Lüdenscheid, Germany
Universitätsklinikum Magdeburg
🇩🇪Magdeburg, Germany
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Philipps-Universität Marburg
🇩🇪Marburg, Germany
Kliniken Maria Hilf Möchengladbach
🇩🇪Möchengladbach, Germany
LMU Klinikum München
🇩🇪München, Germany
Klinikum Rechts der Isar TU München
🇩🇪München, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Klinikum Nürnberg
🇩🇪Nürnberg, Germany
Ortenau Klinikum Offenburg
🇩🇪Offenburg, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Brüderkrankenhaus St. Josef Paderborn
🇩🇪Paderborn, Germany
Klinikum Passau
🇩🇪Passau, Germany
Klinikum Ernst von Bergmann
🇩🇪Potsdam, Germany
Krankenhaus Barmherzige Brüder Regensburg
🇩🇪Regensburg, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Universitätsklinikum Rostock
🇩🇪Rostock, Germany
Agaplesion Diakonieklinikum Rotenburg
🇩🇪Rotenburg/Wümme, Germany
Diakonie-Krankenhaus Schwäbisch-Hall
🇩🇪Schwäbisch-Hall, Germany
Katharinenhospital Stuttgart
🇩🇪Stuttgart, Germany
Diakonissenkrankenhaus Stuttgart
🇩🇪Stuttgart, Germany
Robert-Bosch-Krankenhaus Stuttgart
🇩🇪Stuttgart, Germany
Klinikum Traunstein
🇩🇪Traunstein, Germany
Mutterhaus der Borromäerinnen Trier
🇩🇪Trier, Germany
Krankenhaus d. Barmherzigen Brüder
🇩🇪Trier, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Klinikum Schwarzwald-Baar
🇩🇪Villingen-Schwenningen, Germany
Helios Klinikum Wuppertal
🇩🇪Wuppertal, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Heinrich-Braun Klinikum
🇩🇪Zwickau, Germany