Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01237808
• Other study ID #: AMLSG 15-10
• Status: Completed
• Phase: Phase 3
• Start date: March 2011
• Est. completion date: July 13, 2018

Study information

• Verified date: July 2018
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation ineligible for intensive chemotherapy.

Sample size: 144 patients

Investigator's sites: 50-55 sites in Germany and Austria (2-10 patients per trial site are expected to be included into the trial)

Estimated treatment duration of an individual patient: 8 months (Follow-Up period per patient will last additional 2 years)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: July 13, 2018
• Est. primary completion date: July 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years and older

Eligibility

Inclusion Criteria:

• Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification (including de novo AML, t-AML and s-AML)

• Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories.

• Age > 60 years. There is no upper age limit.

• No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 10 days during the diagnostic screening phase.

• Signed written informed consent

• Men must give their informed consent that they do not father a baby and must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. (while on therapy and for 3 month after the last dose of chemotherapy)

• WHO performance status = 3

• Patients not eligible for intensive chemotherapy according to at least one of the following criteria

• HCT-CI Score >2

• Patient's decision

• age = 75 years

Exclusion Criteria:

The presence of any of the following will exclude a patient from study enrollment:

• All other AML subtypes, in particular those 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

• No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and all other treating physicians about study participation

• Bleeding disorder independent of leukemia

• Uncontrolled infection

• Known positive for HIV, HBV or HCV

• 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)

• 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Cytarabine
in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).
• Etoposide
first treatment cycle Etoposide 50 mg/m²/day, continuously i.v., days 1-3; (total dose 150 mg/m2) treatment cycles 2 to 6 Etoposide 100 mg/day, p.o. or i.v. (over 1 hour), days 1-3; (total dose 300 mg).
• All-trans retinoic acid (ATRA)
in all treatment cycles: ATRA 45 mg/m²/day p.o., days 8-10, ATRA 15 mg/m²/day p.o., days 11-28, with or shortly after meals distributed on 3 doses per day.

Locations

Country	Name	City	State
Germany	Ubbo-Emmius Klinik Aurich	Aurich
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	University Hospital of Bonn	Bonn
Germany	Städtisches Klinikum Braunschweig	Braunschweig
Germany	Klinikum Bremen-Mitte gGmbH	Bremen
Germany	Kliniken Essen Süd, Evangelischs Krankenhaus	Essen
Germany	Klinikum Esslingen	Esslingen
Germany	Medizinische Universitätsklinik	Freiburg
Germany	Medizinisches Versorgungszentrum Osthessen GmbH	Fulda
Germany	Universitätsklinikum Gießen	Gießen
Germany	Wilhelm- Anton- Hospital gGmbH	Goch
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Asklepios Klinik Altona	Hamburg
Germany	University Hospital of Hamburg Eppendorf	Hamburg
Germany	Medical Department III, Hospital of Hannover-Siloah	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Department of Internal Medicine I, University Hospital of Saarland	Homburg
Germany	Staedtisches Klinikum Karlsruhe	Karlsruhe
Germany	Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach	Lebach
Germany	Klinikum der Johannes Gutenberg Universität Mainz	Mainz
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Germany	Pius Hospital Oldenburg	Oldenburg
Germany	Krankenhaus der Barmherzigen Brueder	Regensburg
Germany	Caritas-Klinik St. Theresia	Saarbrücken
Germany	Clinikal Cetner of Stuttgart, Center of Oncology	Stuttgart
Germany	Diakonie-Klinikum Stuttgart	Stuttgart
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	University hospital of Ulm	Ulm
Germany	Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen	Villingen - Schwenningen
Germany	Helios Klinikum Wuppertal	Wuppertal

Sponsors (2)

Lead Sponsor	Collaborator
University of Ulm	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		2 years and 8 months
Secondary	Rate of Complete remission		8 months
Secondary	cumulative incidence of relapse		2 years and 8 months
Secondary	cumulative incidence of death in complete remission		2 years and 8 months
Secondary	event-free survival		2 years and 8 months
Secondary	Rate of early deaths (ED)/hypoplastic deaths (HD)		8 months
Secondary	Type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles	adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.0	8 months
Secondary	Incidence of infection after each treatment cycle		8 months
Secondary	Duration of neutropenia after each treatment cycle		8 months
Secondary	Duration of thrombocytopenia after each treatment cycle		8 months
Secondary	Duration of hospitalization after each treatment cycle		8 months
Secondary	Quality of life	assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics according to Messerer et al.33	2 years and 8 months