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Acute Myeloid Leukemia (AML)Phase 3NCT02172872

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

A Phase 3 study testing standard combination chemotherapy and decitabine in people with Acute Myeloid Leukemia (AML), run by European Organisation for Research and Treatment of Cancer - EORTC at 53 sites in 9 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Acute Myeloid Leukemia (AML)
What is being tested?
standard combination chemotherapy and decitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
606 participants
Where
53 sitesin 9 countries
Study dates
28 Nov 2014to Dec 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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

Who cannot join

  • 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
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  • with intensive chemotherapy or transplantation within the last three years
  • NOTE: The following treatments for previous MDS or MPN are allowed (up to one month before inclusion):
  • 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 any malignancy (except basal and squamous cell carcinoma of the skin) for which the patient received systemic anticancer treatment within 6 months prior to randomization NOTE: Diagnosis of any previous or concomitant malignancy is thus not an exclusion criterion.
  • 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

Trial locations and contacts

53 sites in 9 countries.

53 sites in 9 countries

Italy21 sites

  • Azienda Ospedaliero Universitaria - Ospedali Riuniti

    Ancona, 60020

  • Universita Degli Studi Di Bari - Policlinico

    Bari, 70124

  • Universita di Bologna

    Bologna, 40138

  • Ospedale Regionale A. Pugliese

    Catanzaro, 88100

  • Ospedali Riuniti Foggia

    Foggia, 71100

  • Azienda Ospedaliero - Universitaria Policlinico di Modena

    Modena, 41124

  • Amedeo Avogadro University of Eastern Piedmont-Ospedale Maggiore della Carita

    Novara, 28100

  • La Maddalena S.P.A.

    Palermo, 90146

  • Ospedale San Salvatore

    Pesaro, 61100

  • AUSL Romagna - Ospedale Santa Maria dell Croci

    Ravenna, 48121

  • Arcispedale Di S. Maria Nuova

    Reggio Emilia, 42100

  • AUSL Romagna - Ospedale Infermi di Rimini

    Rimini, 47037

  • H. San Giovanni - Addolorata

    Roma, 00184

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

    Roma, 00189

  • Azienda Ospedallera Universitaria - Policlinico Tor Vergata

    Rome, 00133

  • Instituto Regina Elena / Instituti Fisioterapici Ospitalieri

    Rome, 00144

  • Ospedale San Eugenio

    Rome, 00144

  • Clinica Ematologica dell'Universita di Roma La Sapienza

    Rome, 00161

  • Ospedale Casa Sollievo Della Sofferenza

    San Giovanni Rotondo, 71013

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

    Torino, 10126

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

    Udine, 33100

Other trials in Italy

Germany9 sites

  • Universitätsklinikum Aachen AÖR - Medizinische Fakultät der RWTH

    Aachen, 52074

  • Klinikum Augsburg

    Augsburg, 86156

  • Helios Kliniken - Helios Klinikum Berlin-Buch

    Berlin, 13125

  • Universitätsklinikum Essen

    Essen, 45147

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

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

    Halle, 06120

  • Klinikum Der Phillips - Universität Marburg

    Marburg, 35043

  • Universitaet Rostock - Medizinische Fakultaet

    Rostock, 18055

  • Universitaetsklinikum Tuebingen-Uni Kliniken Berg

    Tübingen, 72076

Other trials in Germany

Netherlands8 sites

  • Rijnstate Hospital

    Arnhem, 6815 AD

  • Reinier De Graaf Gasthuis

    Delft, 2625 AD

  • Unversity Medical Center Groningen

    Groningen, 9713 GZ

  • Medisch Centrum Leeuwarden-Zuid

    Leeuwarden, 8901 BR

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6202 AZ

  • Radboud University Medical Center Nijmegen

    Nijmegen, 6500 HB

  • Canisius-Wilhelmina Ziekenhuis

    Nijmegen, 6532 SZ

  • HagaZiekenhuis - locatie Leyweg

    The Hague, 2545 CH

Other trials in Netherlands

Belgium7 sites

  • A.Z. St. Jan

    Bruges, West-Vlaanderen, 8000

  • Institut Jules Bordet

    Brussels, 1000

  • UZ Antwerpen

    Edegem, Antwerpen, 2650

  • UZ Brussel

    Jette, Brussels Capital, 1090

  • C.H.U. Sart-Tilman

    Liège, 4000

  • CHR De La Citadelle

    Liège, 4000

  • CHR Verviers

    Verviers, Liège, 4800

Other trials in Belgium

France3 sites

  • CHU de Caen - Hôpital Côte de Nacre

    Caen, 14033

  • CHU de Nantes - Hôtel Dieu

    Nantes, 44093

  • Assistance Publique - Hôpitaux de Paris - Hôpital Saint Antoine

    Paris, 75571

Other trials in France

Croatia2 sites

  • Clinical Hospital Merkur

    Zagreb, 10000

  • University Hospital Rebro

    Zagreb, 10000

Other trials in Croatia

Bulgaria1 site

  • National Specialized Hospital for Active Treatment of Haematological Diseases

    Sofia, 1756

Other trials in Bulgaria

Lithuania1 site

  • Vilnius University Hospital Santariskiu Clinics

    Vilnius, 08661

Other trials in Lithuania

Portugal1 site

  • Hospital Escolar Soa Joao

    Porto, PT 4200 - 319

Other trials in Portugal

About this study

Official title: 10-day Decitabine Versus Conventional Chemotherapy ("3+7") Followed by Allografting in AML Patients ≥ 60 Years: a Randomized Phase III Study of the EORTC Leukemia Group, CELG, GIMEMA and German MDS Study Group

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).

Read the detailed description
  • The overall survival (OS) of older AML patients has not been improved during the last decades with intensive chemotherapy based on cytarabine combined with an anthracycline ("3+7").
  • Next generation sequencing technology reveals that mutations in genes involved in epigenetics are frequently mutated in AML (e.g. DNMT3a), suggesting an important role of epigenetics in the pathophysiology of AML. Decitabine (given in a 5-day schedule) has been shown to be superior to low-dose Ara-C.
  • A retrospective analysis revealed that epigenetic therapy (either azacitidine or decitabine) is associated with similar survival rates as intensive chemotherapy in older patients (n=671) with newly diagnosed AML.
  • The recently published encouraging phase 2 data with the 10-day decitabine schedule suggests that decitabine results in similar CR rates compared with intensive chemotherapy. Allogeneic transplantation (alloHCT) also offers the opportunity for cure among older AML patients, therefore treatment strategies should aim to allograft older AML patients.
  • Decitabine treatment can lead to very interesting cure rates when used as "bridging" to allografting.

Based on the data summarized above, we hypothesize that decitabine at a daily dose of 20 mg/m² starting with the 10-day schedule followed by an alloHCT or by continuation of 5-days decitabine cycles is superior to conventional intensive chemotherapy in older AML patients.

Being tested
standard combination chemotherapy, decitabine
Keywords
Newly diagnosed, AML, Elderly, Decitabine, Transplant
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • standard combination chemotherapyDrug

    Also called "3+7" induction chemotherapy, Intensive combined chemotherapy

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

  • decitabineDrug

    Also called Dacogen

    1. Cycle 1: decitabine (20 mg/m²) infusion (1 hr) for 10 days
    2. Cycle 2
    3. if bone marrow (BM) blasts < 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days
    4. if BM blasts >= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days
    5. Cycle 3
    6. if BM blasts < 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days
    7. if BM blasts >= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days
    8. Cycle 4-6: decitabine (20 mg/m²) infusion (1 hr) for 5 days
    9. 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.

Study groups in NCT02172872
Study groupRoleWhat they receive
standard combination chemotherapyActive comparatorNot described
Receives: Drug: standard combination chemotherapy
decitabineExperimentalNot described
Receives: Drug: decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Measured: 4.9 years from first patient in

Secondary outcomes (10)

  1. Occurrence of adverse events (AEs)

    The events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 4.9 years from first patient in

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

    Measured: 4.9 years from first patient in

  3. Transplantation feasibility

    Percentage of patients transplanted

    Measured: 4.9 years from first patient in

  4. Outcome post-transplantation

    PFS, incidence of relapse or progression, and incidence of non-relapse or progression related mortality

    Measured: 4.9 years from first patient in

  5. Health economics impact of each treatment arm

    At the end of each cycle, duration of hospitalization and number of visits (planned or related to event), number of transfusions, growth factor support and intravenous anti-infective are collected

    Measured: 4.9 years from first patient in

  6. Health Related Quality of Life (HRQoL) questionnaires

    EORTC Quality of Life Questionnaire (QLQ-C30) Elderly module (ELD14)

    Measured: 4.9 years from first patient in

  7. Prognostic value of baseline physical and functional conditions on treatment outcome using geriatric assessment tools

    Short physical performance battery (SPPB) and activities of daily living (ADL)

    Measured: 4.9 years from first patient in

  8. complete response (CR/CRi) rate

    All patients who reached complete response (CR) or complete response with incomplete marrow recovery (CRi) after the administration of protocol treatment ("3+7" or decitabine)

    Measured: 4.9 years from first patient in

  9. Overall CR/CRi rate

    All patients who reached CR or CRi, after administration of the protocol treatment ("3+7" or decitabine) or following another salvage/new treatment for AML (other than transplant)

    Measured: 4.9 years from first patient in

  10. Disease-free survival (DFS) from CR or CRi

    The time between the date of CR or CRi and the date of first relapse or death (whatever the cause), whichever occurs first

    Measured: 4.9 years from first patient in

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2014 (estimated)
  2. Study start28 Nov 2014
  3. Primary completion7 Mar 2022
  4. Study completionDec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
606 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02172872
Sponsor's protocol ID
EORTC-1301
Other IDs
2014-001486-27, 2014
Status last verified
Feb 2023
First submitted
19 Jun 2014
Last updated
15 Feb 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 38717861

  • 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.

    PubMed 37914482

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing standard combination chemotherapy and decitabine in people with Acute Myeloid Leukemia (AML), run by European Organisation for Research and Treatment of Cancer - EORTC at 53 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Italy, Germany, Netherlands, Belgium, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: 4.9 years from first patient in). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02172872, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.

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