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
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
adult patients, NPM1 mutation
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Gemtuzumab Ozogamicin (Mylotarg) Type: Drug
Name: standard chemotherapy Type: Drug
Overall Status
Recruiting
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)
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent.

- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.

- Known positive for HIV, active HBV, HCV, or Hepatitis A infection.

- Bleeding disorder independent of leukemia.

- No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
Locations
Universitätsklinikum Innsbruck
Innsbruck, Austria
Status: Recruiting
Krankenhaus der Barmherzigen Schwestern Linz
Linz, Austria
Status: Recruiting
Krankenhaus der Barmherzigen Schwestern Linz Betriebsgesellschaft m.b.H.
Linz, Austria
Status: Recruiting
Contact: Gregor Aschauer, MD
Krankenhaus der Elisabethinen Linz
Linz, Austria
Status: Recruiting
Salzburger Landeskliniken
Salzburg, Austria
Status: Recruiting
Hanuschkrankenhaus Wien
Wien, Austria
Status: Recruiting
Ubbo-Emmius-Klinik Aurich
Aurich, Germany
Status: Recruiting
Helios Klinikum Bad Saarow
Bad Saarow, Germany
Status: Recruiting
Contact: Peter Reichardt, MD
Charité Berlin - Campus Virchow Klinikum
Berlin, Germany
Status: Recruiting
Vivantes Klinikum Neukölln
Berlin, Germany
Status: Recruiting
Knappschaftskrankenhaus Bochum-Langendreer
Bochum, Germany
Status: Recruiting
Universitätsklinikum Bonn
Bonn, Germany
Status: Recruiting
Städtisches Klinikum Braunschweig gGmbH
Braunschweig, Germany
Status: Recruiting
Klinikum Bremen-Mitte
Bremen, Germany
Status: Recruiting
Klinikum Darmstadt
Darmstadt, Germany
Status: Recruiting
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
Status: Recruiting
Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH
Essen, Germany
Status: Recruiting
Klinikum Esslingen
Esslingen, Germany
Status: Recruiting
St. Franziskus Hospital
Flensburg, Germany
Status: Recruiting
Klinikum Frankfurt Höchst GmbH
Frankfurt-Höchst, Germany
Status: Recruiting
Universitätsklinikum Freiburg
Freiburg, Germany
Status: Recruiting
Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, Germany
Status: Recruiting
Universitätsklinikum Gießen
Gießen, Germany
Status: Recruiting
Wilhelm-Anton-Hospital gGmbH Goch
Goch, Germany
Status: Recruiting
Universitätsklinikum Göttingen
Göttingen, Germany
Status: Recruiting
Asklepios Klinik Altona
Hamburg, Germany
Status: Recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Status: Recruiting
Evangelisches Krankenhaus Hamm gGmbH
Hamm, Germany
Status: Recruiting
Klinikum Hanau
Hanau, Germany
Status: Recruiting
KRH Klinikum Hannover-Siloah
Hannover, Germany
Status: Recruiting
Medizinische Hochschule Hannover
Hannover, Germany
Status: Recruiting
SLK-Kliniken GmbH Heilbronn
Heilbronn, Germany
Status: Recruiting
Universitätskliniken des Saarlandes
Homburg, Germany
Status: Recruiting
Städtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany
Status: Recruiting
Universitätsklinikum Kiel
Kiel, Germany
Status: Recruiting
Caritas-Krankenhaus Lebach
Lebach, Germany
Status: Recruiting
Klinikum Lippe-Lemgo
Lemgo, Germany
Status: Recruiting
Klinikum Lüdenscheid
Lüdenscheid, Germany
Status: Recruiting
Universitätsklinikum der Otto-von Guericke Universität Magdeburg
Magdeburg, Germany
Status: Recruiting
Klinikum der Johannes Gutenberg Universität Mainz
Mainz, Germany
Status: Recruiting
Johannes Wesling Klinikum Minden
Minden, Germany
Status: Recruiting
Klinikum rechts der Isar München
München, Germany
Status: Recruiting
Klinikum Schwabing
München, Germany
Status: Recruiting
Lukaskrankenhaus GmbH Neuss
Neuss, Germany
Status: Recruiting
Klinikum Oldenburg gGmbH
Oldenburg, Germany
Status: Recruiting
Klinikum Passau
Passau, Germany
Status: Recruiting
Caritas-Klinik St. Theresia Saarbrücken
Saarbrücken, Germany
Status: Recruiting
Diakonie-Klinikum Stuttgart
Stuttgart, Germany
Status: Recruiting
Klinikum Stuttgart - Katharinenhospital
Stuttgart, Germany
Status: Recruiting
Klinikum Traunstein
Traunstein, Germany
Status: Recruiting
Universitätsklinikum Tübingen
Tübingen, Germany
Status: Recruiting
Universitätsklinikum Ulm
Ulm, Germany
Status: Recruiting
Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
Villingen-Schwenningen, Germany
Status: Recruiting
Helios Klinikum Wuppertal
Wuppertal, Germany
Status: Recruiting
Start Date
February 2010
Completion Date
January 2020
Sponsors
University of Ulm
Source
University of Ulm
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page