Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML

  1. Jaramillo, Sonia ORCID logo
  2. Krisam, Johannes
  3. Le Cornet, Lucian
  4. Kratzmann, Markus
  5. Baumann, Lukas
  6. Sauer, Tim
  7. Crysandt, Martina
  8. Rank, Andreas
  9. Behringer, Dirk
  10. Teichmann, Lino
  11. Görner, Martin
  12. Trappe, Ralf-Ulrich
  13. Röllig, Christoph
  14. Krause, Stefan
  15. Hanoun, Maher
  16. Hopfer, Olaf
  17. Held, Gerhard
  18. Buske, Sebastian
  19. Fransecky, Lars
  20. Kayser, Sabine
  21. Schliemann, Christoph
  22. Schaefer-Eckart, Kerstin
  23. Al-Fareh, Yousef
  24. Schubert, Jörg
  25. Geer, Thomas
  26. Kaufmann, Martin
  27. Brecht, Arne
  28. Niemann, Dirk
  29. Kieser, Meinhard
  30. Bornhäuser, Martin
  31. Platzbecker, Uwe
  32. Serve, Hubert
  33. Baldus, Claudia D.
  34. Müller-Tidow, Carsten
  35. Schlenk, Richard F.

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1000 Titel
  • Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML
1000 Autor/in
  1. Jaramillo, Sonia |
  2. Krisam, Johannes |
  3. Le Cornet, Lucian |
  4. Kratzmann, Markus |
  5. Baumann, Lukas |
  6. Sauer, Tim |
  7. Crysandt, Martina |
  8. Rank, Andreas |
  9. Behringer, Dirk |
  10. Teichmann, Lino |
  11. Görner, Martin |
  12. Trappe, Ralf-Ulrich |
  13. Röllig, Christoph |
  14. Krause, Stefan |
  15. Hanoun, Maher |
  16. Hopfer, Olaf |
  17. Held, Gerhard |
  18. Buske, Sebastian |
  19. Fransecky, Lars |
  20. Kayser, Sabine |
  21. Schliemann, Christoph |
  22. Schaefer-Eckart, Kerstin |
  23. Al-Fareh, Yousef |
  24. Schubert, Jörg |
  25. Geer, Thomas |
  26. Kaufmann, Martin |
  27. Brecht, Arne |
  28. Niemann, Dirk |
  29. Kieser, Meinhard |
  30. Bornhäuser, Martin |
  31. Platzbecker, Uwe |
  32. Serve, Hubert |
  33. Baldus, Claudia D. |
  34. Müller-Tidow, Carsten |
  35. Schlenk, Richard F. |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-11-03
1000 Erschienen in
1000 Quellenangabe
  • 22(1):765
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13063-021-05703-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564967/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial.!##!Methods/design!#!This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 versus GO administered once on day 1 (GO-147 versus GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m!##!Ethics and dissemination!#!Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.!##!Trial status!#!Protocol version: 1st version 20.10.2020, no amendments yet. Study initiation on February 16, 2021. First patient was recruited on April 1st.!##!Trial registration!#!ClinicalTrials.gov NCT04093505 ; EudraCT 2019-003913-32. Registered on October 30, 2018.
1000 Sacherschließung
lokal acute myeloid leukemia
lokal Aged [MeSH]
lokal Study Protocol
lokal Humans [MeSH]
lokal Phenylurea Compounds [MeSH]
lokal glasdegib
lokal Leukemia, Myeloid, Acute/diagnosis [MeSH]
lokal gemtuzumab ozogamicin
lokal Middle Aged [MeSH]
lokal Aminoglycosides/adverse effects [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/adverse effects [MeSH]
lokal Gemtuzumab [MeSH]
lokal measurable residual disease
lokal Induction Chemotherapy [MeSH]
lokal Leukemia, Myeloid, Acute/drug therapy [MeSH]
lokal Benzimidazoles [MeSH]
lokal Antibodies, Monoclonal, Humanized/adverse effects [MeSH]
1000 Liste der Beteiligten
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1000 Erstellt am 2023-11-16T14:53:47.750+0100
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