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

NCT ID: NCT01147939

Last Updated: 2013-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

381 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2013-06-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Acute Myeloid Leukemia (AML)

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Elacytarabine

Group Type EXPERIMENTAL

Elacytarabine

Intervention Type DRUG

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

Investigator's Choice

Group Type ACTIVE_COMPARATOR

Investigator's Choice

Intervention Type DRUG

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

Interventions

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Elacytarabine

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

Intervention Type DRUG

Investigator's Choice

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Clavis Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Rizzieri, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University Medical Center, Durham, NC, USA

Francis J Giles, MD, PhD

Role: STUDY_CHAIR

Cancer Therapy & Reseach Center at the University of Texas Health Science Center San Antonio, TX, USA

Locations

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Scripps Cancer Center Clinical Research

La Jolla, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

UCLA School of Medicine, Division of Hematology/Oncology

Los Angeles, California, United States

Site Status

Rocky Mountain Blood and Bone Marrow Transplant Program

Denver, Colorado, United States

Site Status

Shands at the University of Florida

Gainesville, Florida, United States

Site Status

Winship Cancer Institute at Emory

Atlanta, Georgia, United States

Site Status

The Blood and Marrow Transplant Group of GA

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

St. Francis Hospital and Health Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hopsitals

Iowa City, Iowa, United States

Site Status

LSU Health Sciences Center,

Shreveport, Louisiana, United States

Site Status

Northern New Jersey Cancer Associates

Hackensack, New Jersey, United States

Site Status

New York Presbyterian Hospital, Weill-Cornell Medical College

New York, New York, United States

Site Status

Memorial Sloan-Kettering

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University, Health Sciences Section on Hematology and Oncology

Winston-Salem, North Carolina, United States

Site Status

The Jewish Hospital

Cincinnati, Ohio, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

St. Francis Hospital

Greenville, South Carolina, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Royal North Shore Hopsital

Sydney, New South Wales, Australia

Site Status

Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Box Hill Hospital

Melbourne, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Site Status

Algemeen Ziekenhuis Sint-Jan

Bruges, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

UZ Brussel

Brussels, , Belgium

Site Status

University Hospital Antwerp

Edegem, , Belgium

Site Status

CHU Liège

Liège, , Belgium

Site Status

UCL Mont-Godinne

Yvoir, , Belgium

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

CHU Limoges - Hôpital Dupuytren

Limoges, , France

Site Status

Hopital Edouard Herriot

Lyon, , France

Site Status

Institut J. Paoli and I. Calmettes

Marseille, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hopital Saint Antoine

Paris, , France

Site Status

CHU de Bordeaux - Hopital Haut-Leveque

Pessac, , France

Site Status

CHU de Toulouse - Hôpital Purpan

Toulouse, , France

Site Status

Charité-Campus B. Franklin Med. Klinik Haematology

Berlin, , Germany

Site Status

Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn GmbH

Bonn, , Germany

Site Status

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

Düsseldorf, , Germany

Site Status

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

Mainz, , Germany

Site Status

Universitätsklinikum Münster, Medisinische Klinik & Poliklinik A

Münster, , Germany

Site Status

Universitätsklinikum Rostock

Rostock, , Germany

Site Status

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

Stuttgart, , Germany

Site Status

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

Ulm, , Germany

Site Status

St James's Hospital Dublin

Dublin, , Ireland

Site Status

University Hospital Galway

Galway, , Ireland

Site Status

A.O.U Careggi

Florence, , Italy

Site Status

A.O San Martino

Genova, , Italy

Site Status

Fondazione San Raffaele del Monte Tabor

Milan, , Italy

Site Status

A.O. Cardarelli

Napoli, , Italy

Site Status

Hospital S. Maria delle Croci

Ravenna, , Italy

Site Status

Fondazion Policlin T Vergata

Roma, , Italy

Site Status

Haukeland Universitetssykehus

Bergen, , Norway

Site Status

Oslo University Hospital

Oslo, , Norway

Site Status

St Olavs Hospital

Trondheim, , Norway

Site Status

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, , Poland

Site Status

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

Bucharest, , Romania

Site Status

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

Cluj-Napoca, , Romania

Site Status

St. Spiridon" University Hospital, Hematology Department

Iași, , Romania

Site Status

Hospital de Navarra

Pamplona, Spain, Spain

Site Status

Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Universitario La Princesa

Madrid, , Spain

Site Status

Hospital Universitari Son Dureta

Palma de Mallorca, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario La Fé, Servicio de Hematología

Valencia, , Spain

Site Status

Gartnavel General Hospital: Beatson WOS Cancer Centre

Glasgow, Scotland, United Kingdom

Site Status

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status

Christie Hospital, Haematology and Transplant Day Unit

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Ireland Italy Norway Poland Romania Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 24841975 (View on PubMed)

Related Links

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Other Identifiers

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CP4055-306

Identifier Type: -

Identifier Source: org_study_id