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

September 20, 2013 updated by: Clavis Pharma

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

381

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2065
        • Royal North Shore Hopsital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Alfred Hospital
      • Melbourne, Victoria, Australia, 3128
        • Box Hill Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Belgium
      • Brugge, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan
      • Brussels, Belgium, 1090
        • UZ Brussel
      • Bruxelles, Belgium, 1000
        • Institut Jules Bordet
      • Edegem, Belgium, 2650
        • University Hospital Antwerp
      • Liège, Belgium, 4000
        • Chu Liege
      • Yvoir, Belgium, 5530
        • UCL Mont-Godinne
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G2M9
        • Princess Margaret Hospital
  • France
      • Limoges, France, 87042
        • CHU Limoges - Hopital Dupuytren
      • Lyon, France, 69437
        • Hôpital Edouard Herriot
      • Marseilles, France, 13723
        • Institut J. Paoli and I. Calmettes
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75271
        • Hôpital Saint Antoine
      • Pessac, France, 33604
        • Chu de Bordeaux - Hopital Haut-Leveque
      • Toulouse, France, 31053
        • CHU de Toulouse - Hôpital Purpan
  • Germany
      • Berlin, Germany, 12200
        • Charité-Campus B. Franklin Med. Klinik Haematology
      • Bonn, Germany
        • Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn GmbH
      • Düsseldorf, Germany, 40225
        • Heinrich-Heine Universität Düsseldorf, Klinik für Hämatologie/Onkolog. und Klin. Immunologie
      • Mainz, Germany, 55131
        • III. Medizinische Klinik und Poliklinik;Hämatologie, Onkologie und Pneumologie
      • Münster, Germany, 48149
        • Universitätsklinikum Münster, Medisinische Klinik & Poliklinik A
      • Rostock, Germany, 18057
        • Universitätsklinikum Rostock
      • Stuttgart, Germany, 70736
        • Robert-Bosch-Krankenhaus, Abt.Hämatologie,Onkologie u.Palliativmedizin
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm, Klinik für Innere Medizin III, Comprehensive Cancer Center Ulm (CCCU)
  • Ireland
      • Dublin, Ireland
        • St James's Hospital Dublin
      • Galway, Ireland
        • University Hospital Galway
  • Italy
      • Firenze, Italy, 50134
        • A.O.U Careggi
      • Genova, Italy, 16132
        • A.O San Martino
      • Milano, Italy, 20132
        • Fondazione San Raffaele del Monte Tabor
      • Napoli, Italy, 80131
        • A.O. Cardarelli
      • Ravenna, Italy, 48121
        • Hospital S. Maria delle Croci
      • Roma, Italy, 00133
        • Fondazion Policlin T Vergata
  • Norway
      • Bergen, Norway, 5021
        • Haukeland Universitetssykehus
      • Oslo, Norway, 0027
        • Oslo University Hospital
      • Trondheim, Norway, 7006
        • St Olavs hospital
  • Poland
      • Wroclaw, Poland, 50-367
        • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
  • Romania
      • Bucharest, Romania, 022328
        • Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant
      • Cluj Napoca, Romania, 400124
        • Oncology Institute ,,Ion Chiricuta" Cluj Napoca , Hematology dept.
      • Iasi, Romania, 700111
        • St. Spiridon" University Hospital, Hematology Department
  • Spain
      • Badalona, Spain, 08916
        • Hospital Germans Trias i Pujol
      • Madrid, Spain, 28006
        • Hospital Universitario La Princesa
      • Palma de Mallorca, Spain, 07014
        • Hospital Universitari Son Dureta
      • Pamplona, Spain, 31008
        • Hospital De Navarra
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
      • Valencia, Spain, 46009
        • Hospital Universitario La Fé, Servicio de Hematología
  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Haematology and Oncology Centre
      • Manchester, United Kingdom, M20 4BX
        • Christie Hospital, Haematology and Transplant Day Unit
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Gartnavel General Hospital: Beatson WOS Cancer Centre
  • United States
    • California
      • La Jolla, California, United States, 90095
        • Scripps Cancer Center Clinical Research
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Los Angeles, California, United States, 90095
        • UCLA School of Medicine, Division of Hematology/Oncology
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Blood and Bone Marrow Transplant Program
    • Florida
      • Gainesville, Florida, United States, 32610
        • Shands at the University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute at Emory
      • Atlanta, Georgia, United States, 30342
        • The Blood and Marrow Transplant Group of GA
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46107
        • St. Francis Hospital and Health Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hopsitals
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • LSU Health Sciences Center,
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Northern New Jersey Cancer Associates
    • New York
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital, Weill-Cornell Medical College
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Wake Forest University, Health Sciences Section on Hematology and Oncology
    • Ohio
      • Cincinnati, Ohio, United States, 45236
        • The Jewish Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Western Pennsylvania Hospital
    • South Carolina
      • Greenville, South Carolina, United States, 29601
        • St. Francis Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital, Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Elacytarabine
Drug: Elacytarabine
Elacytarabine 2000 mg/m2/d administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.
Active Comparator: Investigator's Choice
Drug: Investigator's Choice
E.g. cytarabine single agent/combinations, hypomethylating agents, best supportive care (BSC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Until 300 events occur
Time from date of randomisation until the date of death
Until 300 events occur

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission rate
Time Frame: Until 300 events occur
  • 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
Until 300 events occur
Compare number of patients with adverse events (AEs) per study arm as a measure of safety and tolerability
Time Frame: From first dose of study treatment, until 30 days after the last dose (for each patient)
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.
From first dose of study treatment, until 30 days after the last dose (for each patient)
Characterize exposure-response relationships for measures of effectiveness and toxicity
Time Frame: During the first course of elacytarabine
During the first course of elacytarabine

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clavis Pharma

Investigators

  • Principal Investigator: David Rizzieri, MD, Duke University Medical Center, Durham, NC, USA
  • Study Chair: Francis J Giles, MD, PhD, Cancer Therapy & Reseach Center at the University of Texas Health Science Center San Antonio, TX, USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

April 14, 2010

First Submitted That Met QC Criteria

June 21, 2010

First Posted (Estimate)

June 22, 2010

Study Record Updates

Last Update Posted (Estimate)

September 27, 2013

Last Update Submitted That Met QC Criteria

September 20, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP4055-306

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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