"InDACtion" vs "3+7" Induction in AML

NCT02172872 | Unknown Phase 3 DMC

• 2 other identifiers: EORTC-13012014-001486-27
• Study Type: interventional
• Target: 606
• Locations: 9 countries
• Sites: 53

Brief Summary

Older patients with acute myeloid leukemia (AML) have a small (\< 10%) chance of long-term survival. Despite the treatment of elderly AML patients with intensive chemotherapy, the survival has not been improved during the last decades. The purpose of this study is to determine whether frontline therapy with a 10-day decitabine schedule provides a better survival than standard intensive combination chemotherapy in elderly AML patients (\>= 60 years).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Newly diagnosed; AML; Elderly; Decitabine; Transplant

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  4.9 years from first patient in

Secondary Outcomes (10)

• Occurrence of adverse events (AEs)

  4.9 years from first patient in

• Progression-free survival (PFS) from randomization to the date of either first progression, first relapse or death, whichever occurs first

  4.9 years from first patient in

• Transplantation feasibility

  4.9 years from first patient in

• Outcome post-transplantation

  4.9 years from first patient in

• Health economics impact of each treatment arm

  4.9 years from first patient in

Study Arms (2)

standard combination chemotherapy

ACTIVE COMPARATOR

Drug: standard combination chemotherapy

decitabine

EXPERIMENTAL

Drug: decitabine

Interventions

standard combination chemotherapy DRUG

1. Cycle 1 1. daunorubicin (60 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (200 mg/m²) continuous infusion (24 hrs) for 7 days. 2. Cycle 2 1. daunorubicin (45 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (200 mg/m²) continuous infusion (24 hrs) for 7 days. 3. Cycle 3 (mini-ICE) 1. idarubicin (8 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (100 mg/m²) continuous infusion (24 hrs) for 5 days 3. etoposide (100 mg/m²) infusion (1 hr) for 3 days 4. Cycle 4 (mini-ICE) (optional) 1. idarubicin (8 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (100 mg/m²) continuous infusion (24 hrs) for 5 days 3. etoposide (100 mg/m²) infusion (1 hr) for 3 days

Also known as: "3+7" induction chemotherapy, Intensive combined chemotherapy

standard combination chemotherapy

decitabine DRUG

1. Cycle 1: decitabine (20 mg/m²) infusion (1 hr) for 10 days 2. Cycle 2 1. if bone marrow (BM) blasts \< 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days 2. if BM blasts \>= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days 3. Cycle 3 1. if BM blasts \< 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days 2. if BM blasts \>= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days 4. Cycle 4-6: decitabine (20 mg/m²) infusion (1 hr) for 5 days 5. Continuation therapy from Cycle 7 and until 'progression or toxicity': decitabine (20 mg/m²) infusion (1 hr) for 5 days or 3 days Note: All patients considered eligible for transplant should be consolidated with alloHCT once donor is available.

Also known as: Dacogen

decitabine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60 years
• WHO Performance status ≤ 2
• Eligible for standard intensive chemotherapy
• Newly diagnosed AML cytopathologically confirmed to the WHO classification (up to 2 months prior to randomization)
• De novo or secondary AML is allowed
• White blood cell (WBC) count is ≤ 30x10E9/L (measured within 72 hours prior to randomization).
• Laboratory assessments (measured prior to randomization):
• serum glutamate oxaloacetate transaminase (SGOT / ASAT) and serum glutamate pyruvate transaminase (SGPT / ALAT) \< 2.5 x the upper limit of normal range unless considered AML-related
• Total serum bilirubin \< 2.5 x the upper limit of normal range unless considered AML-related or due to Gilbert's syndrome
• Serum creatinine \< 2.5 x the upper limit of normal range unless considered AML-related
• Patients of reproductive potential should use adequate birth control measures, as defined by investigator, during the study treatment period and for at least 3 months after the last study treatment.
• Before patient registration/randomization, written informed consent must be given according to the International Conference of Harmonization good clinical practice (ICH GCP) and national/local regulations

You may not qualify if:

• Presence of acute promyelocytic leukemia (APL, i.e. AML-M3 with t(15;17)(q22;q12); promyelocytic leukemia - retinoic acid receptor-alpha (PML-RARA) fusion gene and cytogenetic variants)
• Presence of blast crisis of chronic myeloid leukemia
• Presence of active central nervous system (CNS) leukemia
• Patients did not receive any prior treatment for AML (relapsed AML is not allowed), such as any antileukemic therapy including investigational agents and hypomethylating agents (decitabine, 5-azacytidine). Treatment with hydroxyurea (HU) is allowed to control the leukocytosis if given preferably for less than 5 days and is stopped at least two days prior to the start of any of the protocol regimens
• Patients received any prior treatment for myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) with:
• hypomethylating agents (decitabine, 5-azacytidine), OR
• with intensive chemotherapy or transplantation within the last three years
• Growth factors, thrombomimetics, immunosuppression (cyclosporin A, steroids, antithymocyte globulin etc.), chelation, interferons, anagrelide
• Lenalidomide, low-dose chemotherapy (low-dose melphalan, HU, low-dose cytarabine etc.), tyrosine-kinase inhibitors, histone deacetylase inhibitors (e.g. valproic acid, panobinostat etc.), mammalian target of rapamycin (mTOR) inhibitors, other experimental treatment that is not based on inhibition of deoxyribonucleic acid (DNA) methyltransferase
• Presence of concomitant severe cardiovascular disease which would make intensive chemotherapy impossible, i.e. uncontrolled arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease, reduced left ventricular function assessed by multigated acquisition (MUGA) scan or echocardiogram
• Presence of active uncontrolled infection
• Presence of any psychological, familial, sociological or geographical condition in the opinion of the investigator potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Janssen Pharmaceuticals: collaborator
• Gruppo Italiano Malattie EMatologiche dell'Adulto: collaborator

Study Sites (53)

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

UZ Brussel

Jette, Brussels Capital, 1090, Belgium

Location

CHR Verviers

Verviers, Liège, 4800, Belgium

Location

A.Z. St. Jan

Bruges, West-Vlaanderen, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

C.H.U. Sart-Tilman

Liège, 4000, Belgium

Location

CHR De La Citadelle

Liège, 4000, Belgium

Location

National Specialized Hospital for Active Treatment of Haematological Diseases

Sofia, 1756, Bulgaria

Location

Clinical Hospital Merkur

Zagreb, 10000, Croatia

Location

University Hospital Rebro

Zagreb, 10000, Croatia

Location

CHU de Caen - Hôpital Côte de Nacre

Caen, 14033, France

Location

CHU de Nantes - Hôtel Dieu

Nantes, 44093, France

Location

Assistance Publique - Hôpitaux de Paris - Hôpital Saint Antoine

Paris, 75571, France

Location

Universitätsklinikum Aachen AÖR - Medizinische Fakultät der RWTH

Aachen, 52074, Germany

Location

Klinikum Augsburg

Augsburg, 86156, Germany

Location

Helios Kliniken - Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetklinikum Halle - Martin Luther Universitaet - Universitaetsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Klinikum Der Phillips - Universität Marburg

Marburg, 35043, Germany

Location

Universitaet Rostock - Medizinische Fakultaet

Rostock, 18055, Germany

Location

Universitaetsklinikum Tuebingen-Uni Kliniken Berg

Tübingen, 72076, Germany

Location

Azienda Ospedaliero Universitaria - Ospedali Riuniti

Ancona, 60020, Italy

Location

Universita Degli Studi Di Bari - Policlinico

Bari, 70124, Italy

Location

Universita di Bologna

Bologna, 40138, Italy

Location

Ospedale Regionale A. Pugliese

Catanzaro, 88100, Italy

Location

Ospedali Riuniti Foggia

Foggia, 71100, Italy

Location

Azienda Ospedaliero - Universitaria Policlinico di Modena

Modena, 41124, Italy

Location

Amedeo Avogadro University of Eastern Piedmont-Ospedale Maggiore della Carita

Novara, 28100, Italy

Location

La Maddalena S.P.A.

Palermo, 90146, Italy

Location

Ospedale San Salvatore

Pesaro, 61100, Italy

Location

AUSL Romagna - Ospedale Santa Maria dell Croci

Ravenna, 48121, Italy

Location

Arcispedale Di S. Maria Nuova

Reggio Emilia, 42100, Italy

Location

AUSL Romagna - Ospedale Infermi di Rimini

Rimini, 47037, Italy

Location

H. San Giovanni - Addolorata

Roma, 00184, Italy

Location

Universita Degli Studi Di Roma La Sapienza - Ospedale Sant'Andrea

Roma, 00189, Italy

Location

Azienda Ospedallera Universitaria - Policlinico Tor Vergata

Rome, 00133, Italy

Location

Instituto Regina Elena / Instituti Fisioterapici Ospitalieri

Rome, 00144, Italy

Location

Ospedale San Eugenio

Rome, 00144, Italy

Location

Clinica Ematologica dell'Universita di Roma La Sapienza

Rome, 00161, Italy

Location

Ospedale Casa Sollievo Della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale Molinette

Torino, 10126, Italy

Location

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" di Udine

Udine, 33100, Italy

Location

Vilnius University Hospital Santariskiu Clinics

Vilnius, 08661, Lithuania

Location

Rijnstate Hospital

Arnhem, 6815 AD, Netherlands

Location

Reinier De Graaf Gasthuis

Delft, 2625 AD, Netherlands

Location

Unversity Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Medisch Centrum Leeuwarden-Zuid

Leeuwarden, 8901 BR, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Radboud University Medical Center Nijmegen

Nijmegen, 6500 HB, Netherlands

Location

Canisius-Wilhelmina Ziekenhuis

Nijmegen, 6532 SZ, Netherlands

Location

HagaZiekenhuis - locatie Leyweg

The Hague, 2545 CH, Netherlands

Location

Hospital Escolar Soa Joao

Porto, PT 4200 - 319, Portugal

Location

Related Publications (2)

• Efficace F, Kicinski M, Coens C, Suciu S, van der Velden WJFM, Noppeney R, Chantepie S, Griskevicius L, Neubauer A, Audisio E, Luppi M, Fuhrmann S, Foa R, Crysandt M, Gaidano G, Vrhovac R, Venditti A, Posthuma EFM, Candoni A, Baron F, Legrand O, Mengarelli A, Fazi P, Vignetti M, Giraut A, Wijermans PW, Huls G, Lubbert M. Decitabine in older patients with AML: quality of life results of the EORTC-GIMEMA-GMDS-SG randomized phase 3 trial. Blood. 2024 Aug 1;144(5):541-551. doi: 10.1182/blood.2023023625.

  PMID: 38717861 DERIVED

• Lubbert M, Wijermans PW, Kicinski M, Chantepie S, Van der Velden WJFM, Noppeney R, Griskevicius L, Neubauer A, Crysandt M, Vrhovac R, Luppi M, Fuhrmann S, Audisio E, Candoni A, Legrand O, Foa R, Gaidano G, van Lammeren-Venema D, Posthuma EFM, Hoogendoorn M, Giraut A, Stevens-Kroef M, Jansen JH, de Graaf AO, Efficace F, Ammatuna E, Vilque JP, Wasch R, Becker H, Blijlevens N, Duhrsen U, Baron F, Suciu S, Amadori S, Venditti A, Huls G; EORTC Leukemia Group, GIMEMA, and German MDS Study Group. 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial. Lancet Haematol. 2023 Nov;10(11):e879-e889. doi: 10.1016/S2352-3026(23)00273-9.

  PMID: 37914482 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Michael Luebbert, MD, PhD

  Universitaetsklinikum Freiburg, Freiburg, Germany

  STUDY CHAIR

• Gerwin G Huls, MD, PhD

  UMCG, Groningen, The Netherlands

  PRINCIPAL INVESTIGATOR

• Pierre W Wijermans, MD

  HagaZiekenhuis, the Hague, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 24, 2014
• Study Start: November 28, 2014
• Primary Completion: March 7, 2022
• Study Completion: December 1, 2023
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

BE (7); NL (8); FR (3); BU (1); IT (21); LI (1); PT (1); DE (9); CR (2)