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Acute Myeloid Leukemia (AML)Phase 3CLAVELANCT01147939

Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)

A Phase 3 study testing Elacytarabine and Investigator's Choice in people with Acute Myeloid Leukemia (AML), run by Clavis Pharma at 73 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of the study is to assess the efficacy and safety of elacytarabine versus investigator's choice treatment in patients with relapsed or refractory acute myeloid leukemia (AML). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia (AML)
What is being tested?
Elacytarabine and Investigator's Choice
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
381 participants
Where
73 sitesin 13 countries
Study dates
Jun 2010to Jun 2013
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older
  • Confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukaemia) who have received two or three previous induction/re-induction regimens or patients of age ≥ 65 with adverse cytogenetics who have received 1-3 previous induction/re-induction regimens. One of the (re-)induction regimens could be stem cell transplantation (SCT) for achievement of remission. Maintenance and consolidation (including SCT) may have been given, but are not counted as previous regimens.
  • Bone marrow aspirates and/or biopsies must contain > 5 % leukaemic blast cells or patient must have biopsy-proven extramedullary AML, or patient's peripheral blood shows occurrence of leukaemic blast cells
  • Patients must
  • have never attained CR or CRi (primary refractory), or
  • have failed initial induction therapy, and have attained CR or CRi after salvage therapy(ies), and then relapsed within < 6 months, or
Show all 14Show fewer
  • have attained CR or CRi after initial induction therapy and relapsed within <12 months, and failed to respond to salvage therapy(ies), or
  • have relapsed after the latest CR or CRi within < 6 months
  • Patients younger than 65 years should have received previous treatment with cytarabine
  • Patients must have recovered from previous bone marrow and/or stem cell transplantation to a stage that the patient can tolerate the study treatment. There is no restriction on number of regimens or type of treatment administered for maintenance or consolidation during previous stages of the disease
  • ECOG performance status (PS) of 0 - 2
  • Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
  • Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last elacytarabine dose
  • Capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form

Who cannot join

  • A history of allergic reactions to egg. A history of allergic reactions of CTCAE grade 3 or 4 to cytarabine
  • Persistent clinically significant toxicities from previous chemotherapy
  • A cancer history that, according to the investigator, might confound the assessment of the study endpoints
  • Known positive status for human immunodeficiency virus (HIV)
  • Pregnant and nursing patients
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
Show all 13Show fewer
  • Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study
  • Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any New York Heart Association (NYHA) functional classification grade 3 or 4
  • Applicable only for patients for whom an anthracycline is part of the selected control treatment: Left ventricular ejection fraction (LVEF) must be ≥ 45 % as measured by MUGA scan or 2D ECHO within 14 days prior to start of therapy. Either method is acceptable for measuring LVEF
  • Applicable only for patients for whom an anthracycline is part of the selected control treatment: The patient should tolerate minimum one course of combination therapy
  • Any anti-leukaemic agents within the last 3 weeks. Hydroxyurea,however, is allowed for up to 12 hours prior to study treatment
  • Any investigational treatment within the last 14 days
  • Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities

Trial locations and contacts

73 sites in 13 countries.

73 sites in 13 countries

United States23 sites
  • Winship Cancer Institute at Emory

    Atlanta, Georgia, 30322

  • The Blood and Marrow Transplant Group of GA

    Atlanta, Georgia, 30342

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • The Jewish Hospital

    Cincinnati, Ohio, 45236

  • Rocky Mountain Blood and Bone Marrow Transplant Program

    Denver, Colorado, 80218

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Shands at the University of Florida

    Gainesville, Florida, 32610

  • St. Francis Hospital

    Greenville, South Carolina, 29601

  • Northern New Jersey Cancer Associates

    Hackensack, New Jersey, 07601

  • St. Francis Hospital and Health Center

    Indianapolis, Indiana, 46107

  • University of Iowa Hopsitals

    Iowa City, Iowa, 52242

  • Scripps Cancer Center Clinical Research

    La Jolla, California, 90095

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90033

  • UCLA School of Medicine, Division of Hematology/Oncology

    Los Angeles, California, 90095

  • Froedtert Hospital, Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • New York Presbyterian Hospital, Weill-Cornell Medical College

    New York, New York, 10021

  • Memorial Sloan-Kettering

    New York, New York, 10065

  • Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania, 15224

  • LSU Health Sciences Center,

    Shreveport, Louisiana, 71103

  • New York Medical College

    Valhalla, New York, 10595

  • Wake Forest University, Health Sciences Section on Hematology and Oncology

    Winston-Salem, North Carolina, 27157-1082

Other trials in United States

Germany8 sites
  • Charité-Campus B. Franklin Med. Klinik Haematology

    Berlin, 12200

  • Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn GmbH

    Bonn

  • Heinrich-Heine Universität Düsseldorf, Klinik für Hämatologie/Onkolog. und Klin. Immunologie

    Düsseldorf, 40225

  • III. Medizinische Klinik und Poliklinik;Hämatologie, Onkologie und Pneumologie

    Mainz, 55131

  • Universitätsklinikum Münster, Medisinische Klinik & Poliklinik A

    Münster, 48149

  • Universitätsklinikum Rostock

    Rostock, 18057

  • Robert-Bosch-Krankenhaus, Abt.Hämatologie,Onkologie u.Palliativmedizin

    Stuttgart, 70736

  • Universitätsklinikum Ulm, Klinik für Innere Medizin III, Comprehensive Cancer Center Ulm (CCCU)

    Ulm, 89081

Other trials in Germany

France7 sites
  • CHU Limoges - Hôpital Dupuytren

    Limoges, 87042

  • Hopital Edouard Herriot

    Lyon, 69437

  • Institut J. Paoli and I. Calmettes

    Marseille, 13723

  • Centre Antoine Lacassagne

    Nice, 06189

  • Hopital Saint Antoine

    Paris, 75271

  • CHU de Bordeaux - Hopital Haut-Leveque

    Pessac, 33604

  • CHU de Toulouse - Hôpital Purpan

    Toulouse, 31053

Other trials in France

Belgium6 sites
  • Algemeen Ziekenhuis Sint-Jan

    Bruges, 8000

  • Institut Jules Bordet

    Brussels, 1000

  • UZ Brussel

    Brussels, 1090

  • University Hospital Antwerp

    Edegem, 2650

  • CHU Liège

    Liège, 4000

  • UCL Mont-Godinne

    Yvoir, 5530

Other trials in Belgium

Italy6 sites
  • A.O.U Careggi

    Florence, 50134

  • A.O San Martino

    Genova, 16132

  • Fondazione San Raffaele del Monte Tabor

    Milan, 20132

  • A.O. Cardarelli

    Naples, 80131

  • Hospital S. Maria delle Croci

    Ravenna, 48121

  • Fondazion Policlin T Vergata

    Roma, 00133

Other trials in Italy

Spain6 sites
  • Hospital Germans Trias i Pujol

    Badalona, 08916

  • Hospital Universitario La Princesa

    Madrid, 28006

  • Hospital Universitari Son Dureta

    Palma de Mallorca, 07014

  • Hospital de Navarra

    Pamplona, Spain, 31008

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario La Fé, Servicio de Hematología

    Valencia, 46009

Other trials in Spain

Australia4 sites
  • Alfred Hospital

    Melbourne, Victoria, 3004

  • Box Hill Hospital

    Melbourne, Victoria, 3128

  • Sir Charles Gairdner Hospital

    Perth, Western Australia, 6009

  • Royal North Shore Hopsital

    Sydney, New South Wales, 2065

Other trials in Australia

Norway3 sites
  • Haukeland Universitetssykehus

    Bergen, 5021

  • Oslo University Hospital

    Oslo, 0027

  • St Olavs Hospital

    Trondheim, 7006

Other trials in Norway

Romania3 sites
  • Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant

    Bucharest, 022328

  • Oncology Institute ,,Ion Chiricuta" Cluj Napoca , Hematology dept.

    Cluj-Napoca, 400124

  • St. Spiridon" University Hospital, Hematology Department

    Iași, 700111

Other trials in Romania

United Kingdom3 sites
  • Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED

  • Gartnavel General Hospital: Beatson WOS Cancer Centre

    Glasgow, Scotland, G12 0YN

  • Christie Hospital, Haematology and Transplant Day Unit

    Manchester, M20 4BX

Other trials in United Kingdom

Ireland2 sites
  • St James's Hospital Dublin

    Dublin

  • University Hospital Galway

    Galway

Other trials in Ireland

Canada1 site
  • Princess Margaret Hospital

    Toronto, Ontario, M5G2M9

Other trials in Canada

Poland1 site
  • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

    Wroclaw, 50-367

Other trials in Poland

About this study

Official title: A Randomised Phase III Study of Elacytarabine vs. Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia

The purpose of the study is to assess the efficacy and safety of elacytarabine versus investigator's choice treatment in patients with relapsed or refractory acute myeloid leukemia (AML).

Read the detailed description

The study investigates the new nucleoside analogue derivative, elacytarabine, as treatment for patients with relapsed or refractory Acute Myeloid Leukemia (AML). To be included in the study, patients must have failed to respond to two or three different therapies for AML, or have obtained remission but then relapsed within a relatively short period of time. Patients of age ≥ 65 with adverse cytogenetics can be included in the study after having received one and up to three previous induction/re-induction therapies.

Elacytarabine is an investigational drug which is not commercially available. It is the elaidic acid ester derivative of cytarabine. Cytarabine is routinely used in the treatment of patients with AML. A substantial portion of AML patients have a deficient uptake of cytarabine, often explained by lack of a transport protein (hENT1) in the leukemic cell membrane. Due to the elaidic acid (a naturally occurring fatty acid), cellular uptake of elacytarabine is independent of this transport protein.

Patients included in the study will be randomized to elacytarabine or control treatment. Since there is no standard therapy for relapsed or refractory AML, there is a list of 7 control treatments and the investigator has to choose one that is locked before randomization.

Elacytarabine is given as a continuous infusion over five days, followed by a rest period of minimum two weeks. Investigator's choice treatment is given according to the specific routine.

After each course response evaluation and a decision on further treatment will be made.

Repeated courses of elacytarabine and control treatment might be needed to attain and/or maintain complete remission or clinical benefit.

After the end of study treatment, all patients will be followed for relapse and survival.

Being tested
Elacytarabine, Investigator's Choice
Keywords
Acute Myeloid Leukaemia, AML, Haematology, Investigator's Choice, Elacytarabine, Refractory or relapsed AML, Phase III, Randomized, CLAVELA, CP4055-306, Elacyt
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.

  • ElacytarabineDrug

    Elacytarabine 2000 mg/m2/d administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.

  • Investigator's ChoiceDrug

    E.g. cytarabine single agent/combinations, hypomethylating agents, best supportive care (BSC)

Study groups in NCT01147939
Study groupRoleWhat they receive
ElacytarabineExperimentalNot described
Receives: Drug: Elacytarabine
Investigator's ChoiceActive comparatorNot described
Receives: Drug: Investigator's Choice

What is being measured

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

  1. Overall survival

    Time from date of randomisation until the date of death

    Measured: Until 300 events occur

Secondary outcomes (3)
  1. Remission rate

    • Remission rate measured by overall response rate (ORR) (i.e. complete remission (CR) and complete remission with incomplete bone marrow recovery (CRi))
    • Remission rate measured by CR
    • Remission duration analysed using cumulative incidence of relapse (CIR) measured from date of CR or CRi

    Measured: Until 300 events occur

  2. Compare number of patients with adverse events (AEs) per study arm as a measure of safety and tolerability

    Summaries will include rates of occurrence of any AEs, rates of AEs by system organ classification (SOC),rates of discontinuation of study treatment due to AEs.

    Measured: From first dose of study treatment, until 30 days after the last dose (for each patient)

  3. Characterize exposure-response relationships for measures of effectiveness and toxicity

    Measured: During the first course of elacytarabine

Timeline

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

  1. First posted22 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionFeb 2013
  4. Study completionJun 2013

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
381 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01147939
Sponsor's protocol ID
CP4055-306
Acronym
CLAVELA
Status last verified
Sep 2013
First submitted
14 Apr 2010
Last updated
27 Sep 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss O, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. doi: 10.1200/JCO.2013.52.8562. Epub 2014 May 19.

    PubMed 24841975

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Elacytarabine and Investigator's Choice in people with Acute Myeloid Leukemia (AML), run by Clavis Pharma at 73 sites in 13 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 14 inclusion and 13 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: finished, as of the sponsor's last update on 27 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, Germany, France, Belgium, Italy and 8 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 (time frame: Until 300 events occur). 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 NCT01147939, which also lists 1 linked publication.

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 27 Sep 2013.

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