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

NCT ID: NCT01237808

Last Updated: 2018-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2018-07-13

Brief 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)

Conditions

Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard arm

6 cycles of chemotherapy (low-dose cytarabine and etoposide) without ATRA

Group Type: ACTIVE_COMPARATOR

Cytarabine

Intervention Type: DRUG

in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).

Etoposide

Intervention Type: DRUG

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).

Investigational arm

6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).

Etoposide

Intervention Type: DRUG

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)

Intervention Type: DRUG

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.

Interventions

Cytarabine

in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).

Intervention Type: DRUG

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).

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 61 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

University of Ulm

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Hartmut Doehner

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hartmut Döhner, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Ulm

Locations

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 am Neckar, , Germany

Medizinische Universitätsklinik

Freiburg im Breisgau, , Germany

Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, , Germany

Universitätsklinikum Gießen

Giessen, , Germany

Wilhelm- Anton- Hospital gGmbH

Goch, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

University Hospital of Hamburg Eppendorf

Hamburg, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Medical Department III, Hospital of Hannover-Siloah

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , 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

Stauferklinikum Schwäbisch Gmünd

Mutlangen, , Germany

Klinikum rechts der Isar der TU Muenchen

München, , 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, , Germany

Countries

Germany

Other Identifiers

AMLSG 15-10

Identifier Type: -

Identifier Source: org_study_id