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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01147939
Other study ID # CP4055-306
Secondary ID
Status Completed
Phase Phase 3
First received April 14, 2010
Last updated September 20, 2013
Start date June 2010
Est. completion date June 2013

Study information

Verified date September 2013
Source Clavis Pharma
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 381
Est. completion date June 2013
Est. primary completion date February 2013
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

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

Locations

Country Name City State
Australia Alfred Hospital Melbourne Victoria
Australia Box Hill Hospital Melbourne Victoria
Australia Sir Charles Gairdner Hospital Perth Western Australia
Australia Royal North Shore Hopsital Sydney New South Wales
Belgium Algemeen Ziekenhuis Sint-Jan Brugge
Belgium UZ Brussel Brussels
Belgium Institut Jules Bordet Bruxelles
Belgium University Hospital Antwerp Edegem
Belgium CHU Liège Liège
Belgium UCL Mont-Godinne Yvoir
Canada Princess Margaret Hospital Toronto Ontario
France CHU Limoges - Hôpital Dupuytren Limoges
France Hopital Edouard Herriot Lyon
France Institut J. Paoli and I. Calmettes Marseilles
France Centre Antoine Lacassagne Nice
France Hopital Saint Antoine Paris
France CHU de Bordeaux - Hopital Haut-Leveque Pessac
France CHU de Toulouse - Hôpital Purpan Toulouse
Germany Charité-Campus B. Franklin Med. Klinik Haematology Berlin
Germany Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn GmbH Bonn
Germany Heinrich-Heine Universität Düsseldorf, Klinik für Hämatologie/Onkolog. und Klin. Immunologie Düsseldorf
Germany III. Medizinische Klinik und Poliklinik;Hämatologie, Onkologie und Pneumologie Mainz
Germany Universitätsklinikum Münster, Medisinische Klinik & Poliklinik A Münster
Germany Universitätsklinikum Rostock Rostock
Germany Robert-Bosch-Krankenhaus, Abt.Hämatologie,Onkologie u.Palliativmedizin Stuttgart
Germany Universitätsklinikum Ulm, Klinik für Innere Medizin III, Comprehensive Cancer Center Ulm (CCCU) Ulm
Ireland St James's Hospital Dublin Dublin
Ireland University Hospital Galway Galway
Italy A.O.U Careggi Firenze
Italy A.O San Martino Genova
Italy Fondazione San Raffaele del Monte Tabor Milano
Italy A.O. Cardarelli Napoli
Italy Hospital S. Maria delle Croci Ravenna
Italy Fondazion Policlin T Vergata Roma
Norway Haukeland Universitetssykehus Bergen
Norway Oslo University Hospital Oslo
Norway St Olavs Hospital Trondheim
Poland Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu Wroclaw
Romania Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant Bucharest
Romania Oncology Institute ,,Ion Chiricuta" Cluj Napoca , Hematology dept. Cluj Napoca
Romania St. Spiridon" University Hospital, Hematology Department Iasi
Spain Hospital Germans Trias i Pujol Badalona
Spain Hospital Universitario La Princesa Madrid
Spain Hospital Universitari Son Dureta Palma de Mallorca
Spain Hospital de Navarra Pamplona
Spain Hospital Universitario de Salamanca Salamanca
Spain Hospital Universitario La Fé, Servicio de Hematología Valencia
United Kingdom Bristol Haematology and Oncology Centre Bristol
United Kingdom Gartnavel General Hospital: Beatson WOS Cancer Centre Glasgow Scotland
United Kingdom Christie Hospital, Haematology and Transplant Day Unit Manchester
United States The Blood and Marrow Transplant Group of GA Atlanta Georgia
United States Winship Cancer Institute at Emory Atlanta Georgia
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States The Jewish Hospital Cincinnati Ohio
United States Rocky Mountain Blood and Bone Marrow Transplant Program Denver Colorado
United States Duke University Medical Center Durham North Carolina
United States Shands at the University of Florida Gainesville Florida
United States St. Francis Hospital Greenville South Carolina
United States Northern New Jersey Cancer Associates Hackensack New Jersey
United States St. Francis Hospital and Health Center Indianapolis Indiana
United States University of Iowa Hopsitals Iowa City Iowa
United States Scripps Cancer Center Clinical Research La Jolla California
United States UCLA School of Medicine, Division of Hematology/Oncology Los Angeles California
United States USC/Norris Comprehensive Cancer Center and Hospital Los Angeles California
United States Froedtert Hospital, Medical College of Wisconsin Milwaukee Wisconsin
United States Sarah Cannon Research Institute Nashville Tennessee
United States Memorial Sloan-Kettering New York New York
United States New York Presbyterian Hospital, Weill-Cornell Medical College New York New York
United States Western Pennsylvania Hospital Pittsburgh Pennsylvania
United States LSU Health Sciences Center, Shreveport Louisiana
United States New York Medical College Valhalla New York
United States Wake Forest University, Health Sciences Section on Hematology and Oncology Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Clavis Pharma

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Overall survival Time from date of randomisation until the date of death Until 300 events occur No
Secondary 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
Until 300 events occur No
Secondary 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. From first dose of study treatment, until 30 days after the last dose (for each patient) Yes
Secondary Characterize exposure-response relationships for measures of effectiveness and toxicity During the first course of elacytarabine No
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