Study of Chemotherapy in Combination With All-trans Retinoic Acid (ATRA) With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia (AML) and Mutant Nucleophosmin-1 (NPM1) Gene Mutation

NCT00893399 | Completed Phase 3 DMC

• 1 other identifier: AMLSG 09-09
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 60

Brief Summary

Randomized Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation. Before Amendment No. 4 (December 2013): Primary Efficacy Objective:

• Evaluation of efficacy based on event-free survival (EFS) after induction and consolidation chemotherapy plus all-trans retinoic acid (ATRA) with or without gemtuzumab ozogamicin (GO) in adult patients with acute myeloid leukemia (AML) and mutant nucleophosmin-1 (NPM1) After Amendment No. 4 (December 2013): Primary Efficacy Objective:
• Evaluation of efficacy based on overall survival (OS) after induction and consolidation chemotherapy plus all-trans retinoic acid (ATRA) with or without gemtuzumab ozogamicin (GO) in adult patients with acute myeloid leukemia (AML) and mutant nucleophosmin-1 (NPM1)

Conditions

Acute Myeloid Leukemia

Keywords

adult patients; NPM1 mutation

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  four years

Secondary Outcomes (8)

• Rates of complete remission after induction therapy (CR)

  not later than 56 days

• Cumulative incidences of relapse (CIR) and death in CR (CID)

  four years

• Event-free survival (EFS)

  four years

• Days in hospital during each cycle and during the whole intervention

  6 months

• Type, frequency, severity, timing and relatedness of AEs and laboratory abnormalities observed during different treatment cycles

  6 months

Study Arms (2)

1

EXPERIMENTAL

chemotherapy in combination with ATRA with gemtuzumab ozogamicin

Drug: Gemtuzumab Ozogamicin (Mylotarg); Drug: standard chemotherapy

2

ACTIVE COMPARATOR

chemotherapy in combination with ATRA without gemtuzumab ozogamicin

Drug: standard chemotherapy

Interventions

Gemtuzumab Ozogamicin (Mylotarg) DRUG

Induction Cycle 1, 2: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after etoposide IVI. No dose reduction is foreseen in elderly (\> 60 yrs) patients. Consolidation 1: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after first dose of high-dose cytarabine. No dose reduction is foreseen in elderly (\> 60 yrs) patients. For all patients experiencing prolonged thrombocytopenia CTC-Grade 3/4 during the first or second induction therapy, which occurs for more than day 35 after start of the cycle, the further cycles of therapy will be administered without Gemtuzumab ozogamicin. Consolidation 2, 3: no GO

1

standard chemotherapy DRUG

Idarubicin, Etoposide, Cytarabine, ATRA, Pegfilgrastim

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification.
• Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories.
• Age ≥ 18 years. There is no upper age limit.
• No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 5 days during the diagnostic screening phase.
• Non-pregnant and non-nursing. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration.
• Female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and within one year after the last dose of chemotherapy.
• Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control: one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap).
• "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.
• Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy.
• Signed written informed consent.

You may not qualify if:

• AML with other recurrent genetic changes (according to WHO 2008):
• AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
• AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
• AML with t(15;17)(q22;q12); PML-RARA (or other translocations involving RARA)
• AML with t(9;11)(p22;q23); MLLT3-MLL (or other translocations involving MLL)
• AML with t(6;9)(p23;q34); DEK-NUP214
• AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1.
• Performance status WHO \> 2.
• Patients with ejection fraction \< 50% by MUGA or ECHO scan within 14 days of day 1.
• Organ insufficiency:
• creatinine \> 1.5x upper normal serum level
• bilirubin, AST or ALP \> 2.5x upper normal serum level, not attributable to AML
• heart failure NYHA III/IV
• severe obstructive or restrictive ventilation disorder.
• Uncontrolled infection.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (60)

Medizinische Universitäts Graz

Graz, 8036, Austria

Location

Universitätsklinikum Innsbruck

Innsbruck, A-6020, Austria

Location

Krankenhaus der Barmherzigen Schwestern Linz Betriebsgesellschaft m.b.H.

Linz, A-4010, Austria

Location

Krankenhaus der Barmherzigen Schwestern Linz

Linz, A-4010, Austria

Location

Krankenhaus der Elisabethinen Linz

Linz, A-4020, Austria

Location

Salzburger Landeskliniken

Salzburg, A-5020, Austria

Location

Hanuschkrankenhaus Wien

Vienna, A-1140, Austria

Location

Klinikum Aschaffenburg-Alzenau

Aschaffenburg, 63739, Germany

Location

Ubbo-Emmius-Klinik Aurich

Aurich, 26603, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Vivantes Klinikum am Urban

Berlin, 10967, Germany

Location

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

Charité Berlin - Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Knappschaftskrankenhaus Bochum-Langendreer

Bochum, 44892, Germany

Location

Universitätsklinikum Bonn

Bonn, 53111, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38114, Germany

Location

Klinikum Bremen-Mitte

Bremen, 28177, Germany

Location

Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH

Essen, 45239, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

St. Franziskus Hospital

Flensburg, 24939, Germany

Location

Klinikum Frankfurt Höchst GmbH

Frankfurt-Höchst, 65929, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, 36043, Germany

Location

Universitätsklinikum Gießen

Giessen, 35392, Germany

Location

Wilhelm-Anton-Hospital gGmbH Goch

Goch, 47574, Germany

Location

Universitätsklinikum Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Evangelisches Krankenhaus Hamm gGmbH

Hamm, 59063, Germany

Location

Klinikum Hanau

Hanau, 63450, Germany

Location

KRH Klinikum Hannover-Siloah

Hanover, 30449, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

SLK-Kliniken GmbH Heilbronn

Heilbronn, 74078, Germany

Location

Universitätskliniken des Saarlandes

Homburg, 66421, Germany

Location

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Universitätsklinikum Kiel

Kiel, 24116, Germany

Location

Caritas-Krankenhaus Lebach

Lebach, 66822, Germany

Location

Klinikum Lippe-Lemgo

Lemgo, 32657, Germany

Location

Klinikum Lüdenscheid

Lüdenscheid, 58515, Germany

Location

Universitätsklinikum der Otto-von Guericke Universität Magdeburg

Magdeburg, 39120, Germany

Location

Klinikum der Johannes Gutenberg Universität Mainz

Mainz, 55131, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Klinikum Schwabing

München, 80804, Germany

Location

Klinikum rechts der Isar München

München, 81675, Germany

Location

Lukaskrankenhaus GmbH Neuss

Neuss, 41464, Germany

Location

Ortenau Klinikum Offenburg Gengenbach

Offenburg, 77654, Germany

Location

Klinikum Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

Caritas-Klinik St. Theresia Saarbrücken

Saarbrücken, 66113, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Schwäbisch Gmünd, 73557, Germany

Location

Klinikum Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

Location

Diakonie-Klinikum Stuttgart

Stuttgart, 70176, Germany

Location

Klinikum Traunstein

Traunstein, 83278, Germany

Location

Krankenhaus der Barmherzigen Brüder

Trier, 54292, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, 78050, Germany

Location

Helios Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

Related Publications (2)

• Miah K, Goeman JJ, Putter H, Kopp-Schneider A, Benner A. Variable Selection via Fused Sparse-Group Lasso Penalized Multi-state Models Incorporating Molecular Data. Biom J. 2025 Dec;67(6):e70087. doi: 10.1002/bimj.70087.

  PMID: 41146443 DERIVED

• Dohner H, Weber D, Krzykalla J, Fiedler W, Kuhn MWM, Schroeder T, Mayer K, Lubbert M, Wattad M, Gotze K, Fransecky L, Koller E, Wulf G, Schleicher J, Ringhoffer M, Greil R, Hertenstein B, Krauter J, Martens UM, Nachbaur D, Samra MA, Machherndl-Spandl S, Basara N, Leis C, Schrade A, Kapp-Schwoerer S, Cocciardi S, Bullinger L, Thol F, Heuser M, Paschka P, Gaidzik VI, Saadati M, Benner A, Schlenk RF, Dohner K, Ganser A; German-Austrian AML Study Group. Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. doi: 10.1016/S2352-3026(23)00089-3. Epub 2023 May 12.

  PMID: 37187198 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hartmut Doehner, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: May 5, 2009
• First Posted: May 6, 2009
• Study Start: May 12, 2010
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: February 27, 2023

Record last verified: 2023-02

Locations

AU (7); DE (53)