Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

RECRUITING

NCT06061094

PHASE2

Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

Sponsor: Goethe University

View on ClinicalTrials.gov

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).

Official title: A Multicentre, Randomized Trial in Adults With de Novo Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia to Assess the Efficacy of Ponatinib Versus Imatinib in Combination With Low-intensity Chemotherapy, to Compare End of Therapy With Indication for SCT Versus TKI, Blinatumomab and Chemotherapy in Optimal Responders and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Key Details

Gender

All

Age Range

18 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

220

Start Date

2023-07-14

Completion Date

2029-07-01

Last Updated

2025-04-29

Healthy Volunteers

Conditions

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Interventions

DRUG

Imatinib

Imatinib 600mg QD plus Chemotherapy

DRUG

Ponatinib

Ponatinib 45 mg QD plus chemotherapy

DRUG

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

OTHER

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.

Inclusion Criteria: * 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) Exclusion Criteria: * 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

Locations (85)

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

Clinical Research Directory

Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (85)