Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT
GMALL-EVOLVE
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)
2 other identifiers
interventional
220
1 country
85
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2023
Longer than P75 for phase_2
85 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 14, 2023
CompletedFirst Submitted
Initial submission to the registry
August 20, 2023
CompletedFirst Posted
Study publicly available on registry
September 29, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2029
April 29, 2025
September 1, 2024
6 years
August 20, 2023
April 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care)
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
up to 4 years from randomization I
Secondary Outcomes (1)
Rate of molecular complete remission at week 11 after consolidation
week 11 after consolidation
Other Outcomes (16)
Probability of remission duration
at 2 years, 3 years, 4 yrs
Cumulative incidence of relapse
at 2 years, 3 years, 4 yrs
Mortality in CR
at 2 years, 3 years, 4 yrs
- +13 more other outcomes
Study Arms (5)
A: Imatinib + low dose chemotherapy
ACTIVE COMPARATORImatinib 600mg QD + low dose chemotherapy induction and consolidation I (Standard Arm of Randomization I)
B: Ponatinib + low dose chemotherapy
EXPERIMENTALPonatinib 45mg QD (reduction to 30mg QD after Induction) + low dose chemotherapy induction and consolidation I (Experimental Arm of Randomization I)
C: Molecular CR: End of therapy with indication for SCT
ACTIVE COMPARATORMolecular CR: End of therapy with indication for SCT (Standard Arm of Randomization II)
D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and Blinatumomab
EXPERIMENTALMolecular 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
EXPERIMENTALMolecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm)
Interventions
Imatinib 600mg QD plus Chemotherapy
Ponatinib 45 mg QD plus chemotherapy
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
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
You may qualify if:
- 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)
You may not qualify if:
- 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
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Goethe Universitylead
- Deutsche Leukämie- & Lymphom-Hilfecollaborator
- German Federal Ministry of Education and Researchcollaborator
Study Sites (85)
Uniklinik RWTH Aachen
Aachen, 52074, Germany
Klinikum Aschaffenburg
Aschaffenburg, 63739, Germany
Klinikum Augsburg
Augsburg, 86156, Germany
Helios Klinikum Bad Saarow
Bad Saarow, 15526, Germany
Klinikum Bayreuth
Bayreuth, 95445, Germany
Vivantes Klinikum am Urban
Berlin, 10967, Germany
Charité Universitätsmedizin Berlin
Berlin, 12220, Germany
Vivantes Klinikum Neukölln
Berlin, 12351, Germany
Helios Klinikum Berlin-Buch
Berlin, 13125, Germany
Charite Berlin Virchow Klinikum
Berlin, 13353, Germany
Evangelisches Krankenhaus Bielefeld
Bielefeld, 33611, Germany
UK Knappschaftskrankenhaus Bochum
Bochum, 44892, Germany
Evangelische Kliniken Bonn
Bonn, 53113, Germany
Universitätsklinikum Bonn
Bonn, 53127, Germany
Städtisches Klinikum Braunschweig
Braunschweig, 38114, Germany
Klinikum Bremen-Mitte
Bremen, 28205, Germany
Klinikum Chemnitz
Chemnitz, 09116, Germany
Universitätsklinikum Köln
Cologne, 50937, Germany
Klinikum Darmstadt
Darmstadt, 64283, Germany
Städtisches Klinikum Dessau
Dessau, 06847, Germany
Klinikum Dortmund
Dortmund, 44137, Germany
St. Johannes Hospital Dortmund
Dortmund, 44137, Germany
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 01307, Germany
Helios Klinikum Duisburg
Duisburg, 47166, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, 40225, Germany
Marien Hospital Düsseldorf
Düsseldorf, 40479, Germany
Universitätsklinikum Erlangen
Erlangen, 91054, Germany
St.-Antonius-Hospital
Eschweiler, 52249, Germany
Universitätsklinikum Essen
Essen, 45147, Germany
Evangelisches Krankenhaus Essen-Werden
Essen, 45239, Germany
Department of Medicine, Hematology and Oncology, Goethe University Hospital Frankfurt
Frankfurt, 60580, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Niels-Stensen-Kliniken Georgsmarienhütte
Georgsmarienhütte, 49124, Germany
Wilhelm-Anton-Hospital
Goch, 47574, Germany
Universitätsmedizin Göttingen
Göttingen, 37075, Germany
Universitätsmedizin Greifswald
Greifswald, 17475, Germany
Klinikum Gütersloh
Gütersloh, 33332, Germany
Katholisches Krankenhaus Hagen
Hagen, 58097, Germany
Universitätsklinikum Halle
Halle, 06120, Germany
Asklepios Klinik St. Georg Hamburg
Hamburg, 20099, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20251, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Marien Hospital Herne
Herne, 44625, Germany
Universitätsklinikum des Saarlandes
Homburg, 66421, Germany
Klinikum Idar-Oberstein
Idar-Oberstein, 55743, Germany
Universitätsklinikum Jena
Jena, 07747, Germany
Städtisches Klinikum Karlsruhe
Karlsruhe, 76133, Germany
St. Vincentius-Kliniken Karlsruhe
Karlsruhe, 76137, Germany
Klinikum Kassel
Kassel, 34125, Germany
Universitätsklinikum Kiel
Kiel, 24105, Germany
Gemeinschaftsklinikum Mittelrhein
Koblenz, 56068, Germany
Universitätsklinikum Leipzig
Leipzig, 04103, Germany
Märkische Kliniken Lüdenscheid
Lüdenscheid, 58515, Germany
Universitätsklinikum Magdeburg
Magdeburg, 39120, Germany
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
Mainz, 55131, Germany
Universitätsklinikum Mannheim
Mannheim, 68167, Germany
Philipps-Universität Marburg
Marburg, 35043, Germany
Kliniken Maria Hilf Möchengladbach
Möchengladbach, 41063, Germany
LMU Klinikum München
München, 81377, Germany
Klinikum Rechts der Isar TU München
München, 81675, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Klinikum Nürnberg
Nuremberg, 90419, Germany
Ortenau Klinikum Offenburg
Offenburg, 77654, Germany
Klinikum Oldenburg
Oldenburg, 26133, Germany
Brüderkrankenhaus St. Josef Paderborn
Paderborn, 33098, Germany
Klinikum Passau
Passau, 94032, Germany
Klinikum Ernst von Bergmann
Potsdam, 14467, Germany
Krankenhaus Barmherzige Brüder Regensburg
Regensburg, 93049, Germany
Universitätsklinikum Regensburg
Regensburg, 93053, Germany
Universitätsklinikum Rostock
Rostock, 18057, Germany
Agaplesion Diakonieklinikum Rotenburg
Rotenburg (Wümme), 27342, Germany
Diakonie-Krankenhaus Schwäbisch-Hall
Schwäbisch Hall, 74523, Germany
Katharinenhospital Stuttgart
Stuttgart, 70174, Germany
Diakonissenkrankenhaus Stuttgart
Stuttgart, 70176, Germany
Robert-Bosch-Krankenhaus Stuttgart
Stuttgart, 70376, Germany
Klinikum Traunstein
Traunstein, 83278, Germany
Mutterhaus der Borromäerinnen Trier
Trier, 54290, Germany
Krankenhaus d. Barmherzigen Brüder
Trier, 54292, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Klinikum Schwarzwald-Baar
Villingen-Schwenningen, 78052, Germany
Helios Klinikum Wuppertal
Wuppertal, 42283, Germany
Universitätsklinikum Würzburg
Würzburg, 97080, Germany
Heinrich-Braun Klinikum
Zwickau, 08060, Germany
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nicola Goekbuget, MD
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
- PRINCIPAL INVESTIGATOR
Fabian Lang, MD
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
- PRINCIPAL INVESTIGATOR
Heike Pfeifer, MD
Department of Medicine, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr. Nicola Gökbuget
Study Record Dates
First Submitted
August 20, 2023
First Posted
September 29, 2023
Study Start
July 14, 2023
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2029
Last Updated
April 29, 2025
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will not share