Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT
NCT ID: NCT06061094
Last Updated: 2025-04-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
220 participants
INTERVENTIONAL
2023-07-14
2029-07-01
Brief Summary
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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).
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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A: Imatinib + low dose chemotherapy
Imatinib 600mg QD + low dose chemotherapy induction and consolidation I (Standard Arm of Randomization I)
Imatinib
Imatinib 600mg QD plus Chemotherapy
B: Ponatinib + low dose chemotherapy
Ponatinib 45mg QD (reduction to 30mg QD after Induction) + low dose chemotherapy induction and consolidation I (Experimental Arm of Randomization I)
Ponatinib
Ponatinib 45 mg QD plus chemotherapy
C: Molecular CR: End of therapy with indication for SCT
Molecular CR: End of therapy with indication for SCT (Standard Arm of Randomization II)
Indication for stem cell transplantation
Patients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.
D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and 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)
Imatinib
Imatinib 600mg QD plus Chemotherapy
Ponatinib
Ponatinib 45 mg QD plus chemotherapy
Blinatumomab
Patients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy
E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of Blina
Molecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm)
Imatinib
Imatinib 600mg QD plus Chemotherapy
Ponatinib
Ponatinib 45 mg QD plus chemotherapy
Blinatumomab
Patients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy
Indication for stem cell transplantation
Patients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.
Interventions
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Imatinib
Imatinib 600mg QD plus Chemotherapy
Ponatinib
Ponatinib 45 mg QD plus chemotherapy
Blinatumomab
Patients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy
Indication for stem cell transplantation
Patients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.
Eligibility Criteria
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Inclusion Criteria
* 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)
Exclusion Criteria
* 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
18 Years
65 Years
ALL
No
Sponsors
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Deutsche Leukämie- & Lymphom-Hilfe
UNKNOWN
German Federal Ministry of Education and Research
OTHER_GOV
Goethe University
OTHER
Responsible Party
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Nicola Goekbuget
Dr. Nicola Gökbuget
Principal Investigators
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Nicola Goekbuget, MD
Role: PRINCIPAL_INVESTIGATOR
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
Fabian Lang, MD
Role: PRINCIPAL_INVESTIGATOR
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
Heike Pfeifer, MD
Role: PRINCIPAL_INVESTIGATOR
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
Locations
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Uniklinik RWTH Aachen
Aachen, , Germany
Klinikum Aschaffenburg
Aschaffenburg, , Germany
Klinikum Augsburg
Augsburg, , Germany
Helios Klinikum Bad Saarow
Bad Saarow, , Germany
Klinikum Bayreuth
Bayreuth, , Germany
Vivantes Klinikum am Urban
Berlin, , 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
Evangelische Kliniken Bonn
Bonn, , Germany
Universitätsklinikum Bonn
Bonn, , Germany
Städtisches Klinikum Braunschweig
Braunschweig, , Germany
Klinikum Bremen-Mitte
Bremen, , Germany
Klinikum Chemnitz
Chemnitz, , Germany
Universitätsklinikum Köln
Cologne, , Germany
Klinikum Darmstadt
Darmstadt, , Germany
Städtisches Klinikum Dessau
Dessau, , 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 im Breisgau, , Germany
Niels-Stensen-Kliniken Georgsmarienhütte
Georgsmarienhütte, , Germany
Wilhelm-Anton-Hospital
Goch, , Germany
Universitätsmedizin Göttingen
Göttingen, , Germany
Universitätsmedizin Greifswald
Greifswald, , 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
Medizinische Hochschule Hannover
Hanover, , 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 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
Nuremberg, , 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
Countries
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Central Contacts
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Facility Contacts
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Related Links
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Lang et al, Oncol Res Treat 2024;47:430-433
Other Identifiers
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2022-000760-21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GMALL-EVOLVE
Identifier Type: -
Identifier Source: org_study_id
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