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

Phase 3

Completed

• Conditions: Acute Myeloid Leukemia (AML)
• Interventions: Drug: Cytarabine; Drug: Etoposide; Drug: All-trans retinoic acid (ATRA)

• Registration Number: NCT01237808
• Lead Sponsor: University of Ulm

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)

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-11-09
• Study First Submitted QC: 2010-11-09
• Study First Posted: 2010-11-10
• Study Start: 2011-03
• Status Verified: 2018-07
• Primary Completion: 2018-07-13
• Study Completion: 2018-07-13
• Last Update Submitted: 2018-07-31
• Last Update Posted: 2018-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard arm	Cytarabine	6 cycles of chemotherapy (low-dose cytarabine and etoposide) without ATRA
Investigational arm	Cytarabine	6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)
Investigational arm	Etoposide	6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)
Investigational arm	All-trans retinoic acid (ATRA)	6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)
Standard arm	Etoposide	6 cycles of chemotherapy (low-dose cytarabine and etoposide) without ATRA

Primary Outcome Measures

Name	Time	Method
overall survival	2 years and 8 months

Secondary Outcome Measures

Name	Time	Method
Rate of Complete remission	8 months
cumulative incidence of relapse	2 years and 8 months
event-free survival	2 years and 8 months
Rate of early deaths (ED)/hypoplastic deaths (HD)	8 months
cumulative incidence of death in complete remission	2 years and 8 months
Type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles	8 months	adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.0
Incidence of infection after each treatment cycle	8 months
Duration of neutropenia after each treatment cycle	8 months
Duration of thrombocytopenia after each treatment cycle	8 months
Duration of hospitalization after each treatment cycle	8 months
Quality of life	2 years and 8 months	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

Trial Locations

Locations (33)

Ubbo-Emmius Klinik Aurich; 🇩🇪 Aurich, Germany

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Medizinische Universitätsklinik; 🇩🇪 Freiburg, Germany

Medizinisches Versorgungszentrum Osthessen GmbH; 🇩🇪 Fulda, Germany

Klinikum Bremen-Mitte gGmbH; 🇩🇪 Bremen, Germany

University Hospital of Bonn; 🇩🇪 Bonn, Germany

Kliniken Essen Süd, Evangelischs Krankenhaus; 🇩🇪 Essen, Germany

Städtisches Klinikum Braunschweig; 🇩🇪 Braunschweig, Germany

Klinikum Esslingen; 🇩🇪 Esslingen, Germany

Universitätsmedizin Göttingen; 🇩🇪 Göttingen, Germany

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

Medical Department III, Hospital of Hannover-Siloah; 🇩🇪 Hannover, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen; 🇩🇪 Villingen - Schwenningen, Germany

Department of Internal Medicine I, University Hospital of Saarland; 🇩🇪 Homburg, Germany

Staedtisches Klinikum Karlsruhe; 🇩🇪 Karlsruhe, Germany

Helios Klinikum Wuppertal; 🇩🇪 Wuppertal, Germany

Caritas-Klinik St. Theresia; 🇩🇪 Saarbrücken, Germany

Diakonie-Klinikum Stuttgart; 🇩🇪 Stuttgart, Germany

Clinikal Cetner of Stuttgart, Center of Oncology; 🇩🇪 Stuttgart, Germany

Krankenhaus der Barmherzigen Brüder Trier; 🇩🇪 Trier, Germany

University hospital of Ulm; 🇩🇪 Ulm, Germany

Universitätsklinikum Gießen; 🇩🇪 Gießen, Germany

Wilhelm- Anton- Hospital gGmbH; 🇩🇪 Goch, Germany

SLK-Kliniken Heilbronn GmbH; 🇩🇪 Heilbronn, Germany

Klinikum der Johannes Gutenberg Universität Mainz; 🇩🇪 Mainz, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach; 🇩🇪 Lebach, Germany

Stauferklinikum Schwäbisch Gmünd; 🇩🇪 Mutlangen, Germany

Klinikum rechts der Isar der TU Muenchen; 🇩🇪 Muenchen, Germany

Krankenhaus der Barmherzigen Brueder; 🇩🇪 Regensburg, Germany

Pius Hospital Oldenburg; 🇩🇪 Oldenburg, Germany

University Hospital of Hamburg Eppendorf; 🇩🇪 Hamburg, Germany