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

NCT01147939 | Completed Phase 3 DMC

• 1 other identifier: CP4055-306
• Study Type: interventional
• Target: 381
• Locations: 13 countries
• Sites: 73

Brief 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).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from date of randomisation until the date of death

  Until 300 events occur

Secondary Outcomes (3)

• Remission rate

  Until 300 events occur

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

  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

  During the first course of elacytarabine

Study Arms (2)

Elacytarabine

EXPERIMENTAL

Drug: Elacytarabine

Investigator's Choice

ACTIVE COMPARATOR

Drug: Investigator's Choice

Interventions

Elacytarabine DRUG

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

Elacytarabine

Investigator's Choice DRUG

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

Investigator's Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Clavis Pharma: lead

Study Sites (73)

Scripps Cancer Center Clinical Research

La Jolla, California, 90095, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90033, United States

Location

UCLA School of Medicine, Division of Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Rocky Mountain Blood and Bone Marrow Transplant Program

Denver, Colorado, 80218, United States

Location

Shands at the University of Florida

Gainesville, Florida, 32610, United States

Location

Winship Cancer Institute at Emory

Atlanta, Georgia, 30322, United States

Location

The Blood and Marrow Transplant Group of GA

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

St. Francis Hospital and Health Center

Indianapolis, Indiana, 46107, United States

Location

University of Iowa Hopsitals

Iowa City, Iowa, 52242, United States

Location

LSU Health Sciences Center,

Shreveport, Louisiana, 71103, United States

Location

Northern New Jersey Cancer Associates

Hackensack, New Jersey, 07601, United States

Location

New York Presbyterian Hospital, Weill-Cornell Medical College

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering

New York, New York, 10065, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University, Health Sciences Section on Hematology and Oncology

Winston-Salem, North Carolina, 27157-1082, United States

Location

The Jewish Hospital

Cincinnati, Ohio, 45236, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Francis Hospital

Greenville, South Carolina, 29601, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal North Shore Hopsital

Sydney, New South Wales, 2065, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

Algemeen Ziekenhuis Sint-Jan

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

University Hospital Antwerp

Edegem, 2650, Belgium

Location

CHU Liège

Liège, 4000, Belgium

Location

UCL Mont-Godinne

Yvoir, 5530, Belgium

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

CHU Limoges - Hôpital Dupuytren

Limoges, 87042, France

Location

Hopital Edouard Herriot

Lyon, 69437, France

Location

Institut J. Paoli and I. Calmettes

Marseille, 13723, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital Saint Antoine

Paris, 75271, France

Location

CHU de Bordeaux - Hopital Haut-Leveque

Pessac, 33604, France

Location

CHU de Toulouse - Hôpital Purpan

Toulouse, 31053, France

Location

Charité-Campus B. Franklin Med. Klinik Haematology

Berlin, 12200, Germany

Location

Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn GmbH

Bonn, Germany

Location

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

Düsseldorf, 40225, Germany

Location

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

Mainz, 55131, Germany

Location

Universitätsklinikum Münster, Medisinische Klinik & Poliklinik A

Münster, 48149, Germany

Location

Universitätsklinikum Rostock

Rostock, 18057, Germany

Location

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

Stuttgart, 70736, Germany

Location

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

Ulm, 89081, Germany

Location

St James's Hospital Dublin

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

A.O.U Careggi

Florence, 50134, Italy

Location

A.O San Martino

Genova, 16132, Italy

Location

Fondazione San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

A.O. Cardarelli

Napoli, 80131, Italy

Location

Hospital S. Maria delle Croci

Ravenna, 48121, Italy

Location

Fondazion Policlin T Vergata

Roma, 00133, Italy

Location

Haukeland Universitetssykehus

Bergen, 5021, Norway

Location

Oslo University Hospital

Oslo, 0027, Norway

Location

St Olavs Hospital

Trondheim, 7006, Norway

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, 50-367, Poland

Location

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

Bucharest, 022328, Romania

Location

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

Cluj-Napoca, 400124, Romania

Location

St. Spiridon" University Hospital, Hematology Department

Iași, 700111, Romania

Location

Hospital de Navarra

Pamplona, Spain, 31008, Spain

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Hospital Universitari Son Dureta

Palma de Mallorca, 07014, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario La Fé, Servicio de Hematología

Valencia, 46009, Spain

Location

Gartnavel General Hospital: Beatson WOS Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Christie Hospital, Haematology and Transplant Day Unit

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24841975 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

5'-oleoyl cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• David Rizzieri, MD

  Duke University Medical Center, Durham, NC, USA

  PRINCIPAL INVESTIGATOR

• Francis J Giles, MD, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: June 22, 2010
• Study Start: June 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 27, 2013

Record last verified: 2013-09

Locations

FR (7); BE (6); NO (3); US (23); IE (2); AU (4); ES (6); CA (1); DE (8); PL (1); RO (3); GB (3); IT (6)