Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study

October 12, 2010 updated by: Antisoma Research

Phase III Open-Label Randomized Study of Amonafide L-Malate in Combination With Cytarabine Compared to Daunorubicin in Combination With Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- The ACCEDE Study

Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML.

The purpose of this study is to assess the relative efficacy and safety of amonafide in combination with cytarabine compared to daunorubicin with cytarabine in subjects with documented secondary AML.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

420

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

  • Argentina
      • Buenos Aires, Argentina, B1900AXI
        • Hospital Italiano de la Plata
      • Ciudad Autónoma de Bs. As., Argentina, C1406FWY
        • Hospital General de Agudos "Dr. Teodoro Alvarez"
      • Ciudad Autónoma de Bs. As., Argentina, C1437JCP
        • Clinical Hematology Service
      • Cordoba, Argentina
        • Hospital Provincial de Córdoba
      • Rosario - Santa Fe, Argentina, S2000DSU
        • Sanatorio Parque
  • Australia
    • Australian Capital Territory
      • Garran, Australian Capital Territory, Australia, 2605
        • The Canberra Hospital
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • Box Hill, Victoria, Australia
        • Box Hill Hospital
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Austria
      • Graz, Austria, 8036
        • LKH-Universitats Klinikum Graz
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg
      • St. Polten, Austria, 3100
        • Landesklinikum St. Pölten
  • Belgium
      • Brugge, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Gent, Belgium, 9000
        • University Hospital Gent
      • Yvoir, Belgium, 5530
        • Ucl de Mont-Godinne
  • Canada
      • Halifax, Canada, B3H 2Y9
        • QEII Center for Clinical Research
      • Ottawa, Canada, K1H 8L6
        • The Ottawa Hospital - General Campus
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Health Sciences Centre
  • Chile
      • Santiago, Chile, 7530204
        • Hospital Santa Maria
      • Santiago, Chile, 7571831
        • Hospital Dipreca
      • Viña del Mar, Chile, 2570017
        • Hospital Dr. Gustavo Fricke
  • Czech Republic
      • Prague, Czech Republic, 100 34
        • University Hospital Kralovske Vinohrady Prague
      • Prague, Czech Republic, 128 08
        • General University Hospital Prague
      • Prague, Czech Republic
        • Institute of Haematology and Blood Transfusion Prague
  • Ecuador
      • Guayaquil, Ecuador
        • Instituto Ecuatoriano de Seguridad Social Hospital Regional Teodoro Maldonado Carbó
      • Quito, Ecuador
        • Hospital Carlos Andrade Marin
      • Quito, Ecuador
        • Hospital Militar
  • Estonia
      • Tallinn, Estonia, 13419
        • North Estonia Medical Centre Foundation
  • France
      • Amiens, France, 80054
        • Hopital Sud
      • Lyon, France, 69437
        • Hôpital Edouard HERRIOT
      • Paris, France, 75004
        • Hopital-DIEU
      • Pessac, France, 33604
        • Hôpital du Haut Lévêque
      • Tours, France, 37044
        • Hopital Bretonneau - CHRU de Tours
    • Le Cheaney
      • Versailles, Le Cheaney, France, 78150
        • Hopital de Versailles
  • Germany
      • Berlin, Germany, 12200
        • Charite - Campus Benjamin Franklin
      • Berlin, Germany, 13353
        • Campus Virchow Klinikum
      • Bonn, Germany, 53113
        • Evangelische Kliniken GmbH
      • Eschweiler, Germany, 52249
        • St Antonius Hospital
      • Essen, Germany, 45122
        • Universitätsklinikum Essen
      • Frankfurt, Germany, 65929
        • Stadtische Kliniken Frankfurt
      • Hamburg, Germany, 22763
        • Asklepios Kliniken Altona
      • Hannover, Germany, 30625
        • Medizin Hochschule Hannover
      • Kiel, Germany, 24116
        • Universitatsklinikum Schleswig-Holstein
      • Leverkusen, Germany, 51375
        • Klinikum Leverkusen
      • Lüdenscheid, Germany, 58515
        • Markische Kliniken GmbH Klinikim Ludenscheid
      • Mannheim, Germany, D-68167
        • Universitatsmedizin Mannheim
  • Hungary
      • Budapest, Hungary, 1097
        • Szent Istvan and Szent Laszlo Corporate Hospital - Out-patient Clinic of the Municipality Government
      • Győr, Hungary, 9024
        • Petz Aladar County Teaching Hospital
      • Kaposvár, Hungary, 7400
        • Kaposi Mór County Teaching Hospital
      • Pecs, Hungary
        • University of Pécs
  • Israel
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center
      • Tel Hashomer, Israel, 52621
        • Chaim Sheba Medical Center
  • Italy
      • Brescia, Italy, 25123
        • University of Brescia
      • Firenze, Italy, 50134
        • A.O.U Careggi
      • Genova, Italy, 16132
        • A.O.U San Martino
      • Napoli, Italy, 80131
        • A.O. Cardarelli
      • Pesaro, Italy, 61100
        • A.O. San Salvatore
      • Pisa, Italy, 56125
        • A.O.U Pisana Santa Chiara
      • Roma, Italy, 00161
        • Università degli studi di Roma "La Sapienza"
      • Rome, Italy, 00144
        • Ospedale S. Eugenio
      • Rozzano, Italy, 20089
        • Istituto Clinico Humanitas
  • Korea, Republic of
      • Busan, Korea, Republic of, 614-735
        • Inje University Busan Paik Hospital
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center
      • Seoul, Korea, Republic of, 158-710
        • Ewha Womans University Mokdong Hospital
      • Seoul, Korea, Republic of, 110-799
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 120-752
        • Severance Hospital in YUHS
      • Suwon, Korea, Republic of, 443-721
        • Ajou University Hospital
  • Poland
      • Bialystok, Poland, 15-276
        • Teaching Hospital of the Medical University in Bialystok
      • Gdansk, Poland, 80-952
        • Academic Clinical Centre - Teaching Hospital of the Medical University of Gdansk
      • Lodz, Poland, 93-513
        • Nicolaus Copernicus Provincial Specialist Hospital in Lodz
      • Opole, Poland, 45-372
        • Provincial Hospital in Opole
      • Poznan, Poland, 61-833
        • Poznan Stare Miasto Health Care Facility
      • Slupsk, Poland, 76-200
        • Janusz Korczak Provincial Specialist Hospital
      • Warsaw, Poland, 02-776
        • Institute of Hematology and Transfusiology
      • Warsaw, Poland, 00-909
        • Military Institue of Health Services
      • Wroclaw, Poland, 50-369
        • Independent Public University Hospital No. 1 in Wroclaw
  • Romania
      • Baia Mare, Romania, 430031
        • Dr. Constantin Opris County Emergency Hospital, Internal Medicine Department
      • Brasov, Romania, 500236
        • Brasov County Emergency Clinical Hospital
      • Bucharest, Romania, 022328
        • Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant
      • Bucharest, Romania, 030171
        • Coltea Clinical Hospital
      • Bucharest, Romania, 020125
        • Colentina Clinical Hospital, Internal Medicine Department
      • Sibiu, Romania, 550245
        • Sibiu County Clinical Hospital, Internal Clinic II
  • Russian Federation
      • Cherepovets, Russian Federation, 162627
        • Municipal Medical Institution Municipal Hospital #1
      • Ekaterinburg, Russian Federation, 620102
        • State Medical Institution Sverdlovsk Regional Clinical Hospital #1
      • Irkutsk, Russian Federation, 664079
        • State Medical Institution Irkutsk Regional Clinical Hospital
      • Khabarovsk, Russian Federation, 680009
        • State Medical Institution Territorial Clinical Hospital #1
      • Krasnodar, Russian Federation, 350040
        • State Medical Institution Territorial Clinical Oncological Center
      • Moscow, Russian Federation, 115478
        • State Institution Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences
      • Moscow, Russian Federation, 125101
        • Moscow State Medical Institution Municipal
      • Perm, Russian Federation, 614010
        • Municipal Medical Institution
      • Rostow Am Don, Russian Federation
        • State Higher Educational Instution Rostov State
      • St. Petersburg, Russian Federation, 194291
        • State Medical Institution Leningrad Regional Clinical Hospital
      • St. Petersburg, Russian Federation, 197101
        • State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
      • St. Petersburg, Russian Federation
        • Federal Center of Heart, Blood and Endocrinology
    • Republic of Karelia
      • Petrozavodsk, Republic of Karelia, Russian Federation, 185014
        • State Medical Institution Republican Hospital n.a. V.A. Baranov
  • Spain
      • Badalona, Spain, 08916
        • Hospital Germans Trias i Pujol
      • Barcelona, Spain, 08003
        • Hospital Del Mar
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Barcelona, Spain, 08041
        • Hospital de La Santa Creu i Sant Pau
      • Barcelona, Spain, 08036
        • Hospital Clinic I Provinicial
      • Valencia, Spain
        • Hospital Universitario La Fe
  • Taiwan
      • Changhua, Taiwan, 500
        • Changhua Christian Hospital (CCH)
      • Taichung City, Taiwan, 404
        • Chinese Medical University Hospital (CMUH)
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital (NCKUH)
      • Taipei, Taiwan, 104
        • MacKay Memorial Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital (NTUH)
      • Taipei, Taiwan, 112
        • Veterans General Hospital Taipei (VGH-TP)
    • Kaohsiung Hsien
      • Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan, 83301
        • Chang Gung Memorial Hospital Kao Hsiung Branch
  • Ukraine
      • Cherkasy, Ukraine, 18009
        • Public Institution 'Cherkasy Regional Oncology Center'
      • Dnipropetrovsk, Ukraine, 49102
        • Dnipropetrovsk City General Clinical Hospital #4
      • Ivano-Frankivsk, Ukraine, 76018
        • Ivano-Frankivsk State Medical University
      • Khmelnytsky, Ukraine, 29000
        • Khmelnytsky Regional Hospital
      • Lviv, Ukraine, 79044
        • State Institution 'Institute of Blood Pathology and Transfusion Medicine under the UAMS'
      • Mykolaiv, Ukraine, 54058
        • Mykolaiv Regional Clinical Hospital
      • Odesa, Ukraine, 65025
        • Odesa Regional Clinical Hospital
      • Poltava, Ukraine
        • Ukrainian Medical Academy of Dentistry
      • Vinnytsya, Ukraine, 21018
        • M.I. Pyrohov Vinnytsya Regional Clinical Hospital
      • Zhytomyr, Ukraine, 10013
        • O.F. Herbachevsky Zhytomyr Regional Clinical Hospital
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
      • Oxford, United Kingdom, OX3 9DLJ
        • Churchill Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • University Hospital of Wales
  • United States
    • California
      • Los Angelas, California, United States, 90095
        • UCLA Medical Center
      • Los Angeles, California, United States, 90033
        • Univ of Southern California Comprehensive Cancer Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Health Sciences Center
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Blood and Marrow Transplant Program
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
      • Atlanta, Georgia, United States, 30342
        • The Blood and Marrow Transplant Group of GA
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern University School Of Medicine
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • LSU Health Sciences Center, Feist-Weiller Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02114
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University Of Michigan Cancer Center
      • Lansing, Michigan, United States, 48910
        • Michigan State University
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Lake Success, New York, United States, 11042
        • Northshore Hospital - Monter Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27707
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Taussig Cancer Center, Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17036
        • Penn State Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15224
        • Western Pennsylvania Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02908
        • Roger Williams Medical Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Cancer Center Of The Carolinas
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Utah
      • Salt Lake City, Utah, United States, 84103
        • Intermountain Healthcare

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:

  • Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with FAB classification other than M3 (Acute Promyelocytic Leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy;
  • Either: Known and documented exposure to specific leukemogenic therapy of a specified nature for a non-myeloid condition; OR Documented diagnosis of MDS according to WHO criteria for at least 3 months prior to study entry, with prior bone marrow aspirate, biopsy and peripheral blood smear documenting MDS available to be submitted for subsequent central pathology review.
  • Age 18 years or older;
  • Eastern Cooperative Oncology Group (ECOG) performance score =< 2;
  • Fertile sexually active patients (men and women) must use an effective method of contraception which must be continued throughout the study.
  • Women of childbearing potential must have a negative serum pregnancy test.
  • Left Ventricular Ejection Fraction (LVEF) >= 50%, as determined by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO) within 14 days prior to administration of 1st dose of remission induction chemotherapy;
  • Adequate renal function as evidenced by the following laboratory test, obtained within 10 days prior to administration of 1st dose of remission induction chemotherapy: Serum creatinine =< 1.5 x ULN;
  • Adequate hepatic function as evidenced by the following laboratory tests, obtained within 10 days prior to administration of 1st dose of remission induction chemotherapy (unless attributed to hepatic involvement with AML): Total serum bilirubin =< 1.5 x ULN;Serum AST and ALT =< 1.5 x ULN;
  • Ability of the patient to participate fully in all aspects of this clinical trial;
  • Written Informed Consent and HIPAA authorization (USA sites only) must be obtained and documented.

Exclusion Criteria:

  • Histologic diagnosis of FAB M3 Acute Promyelocytic Leukemia;
  • Clinically active CNS leukemia;
  • Prior induction therapy for AML;
  • Known HIV positive;
  • Known active hepatitis B or C, or any other active liver disease;
  • Patients with parenchymal abnormality on screening chest x-ray must have no evidence of pulmonary infection on chest tomography (CT) prior to starting remission induction therapy.
  • Any major surgery or radiation therapy within 4 weeks prior to study entry;
  • Prior cytotoxic chemotherapy for MDS within 4 weeks prior to study entry (patients with rapidly rising blast count may be enrolled within 4 weeks of prior cytotoxic chemotherapy with waiver from the Medical Monitor);
  • Persistent chronic non-hematologic toxicity (other than alopecia) greater than grade 1 from prior therapy for MDS;
  • Serious concomitant illnesses (for example, pulmonary infiltrate, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart failure AHA class 2 or greater, uncontrolled hypertension, uncontrolled diabetes, actively bleeding gastric ulcer, etc.), which in the investigator's opinion would not make the patient a good candidate for the trial;
  • Pregnant or breast feeding;
  • History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide, cytarabine or daunorubicin;
  • Prior enrollment in this trial;
  • Any other known condition (e.g., familial, sociological, or geographical) or behavior (including substance dependence or abuse, psychological or psychiatric illness), which in the investigator's opinion would make the patient a poor candidate for the trial.

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: Arm A
Amonafide in Combination with Cytarabine
Drug: Amonafide and Cytarabine
Amonafide: 600 mg/m2 IV over 4 hours daily on Days 1-5 (up to max. 2 courses) Cytarabine: 200 mg/m2 IV continuous infusion daily on Days 1-7 (up to max. 2 courses)
Active Comparator: Arm B
Daunorubicin in Combination with Cytarabine
Drug: Daunorubicin and Cytarabine
Daunorubicin: 45 mg/m2 over 30 minutes daily on days 1-3 (up to max. of 2 courses) Cytarabine: 200 mg/m2 IV continuous infusion daily on days 1-7 (up to max. of 2 courses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of CR + CRi (which includes CRc and CRd) will be determined by assessing the proportion of patients who achieved CR or CRi among all evaluable patients.
Time Frame: Course 1/Course 2 Day 37 bone marrow assessments and confirmation bone marrow 30 days later
Course 1/Course 2 Day 37 bone marrow assessments and confirmation bone marrow 30 days later

Secondary Outcome Measures

Outcome Measure
Time Frame
Median duration of remission and median duration of disease free survival.
Time Frame: Follow-up visits following post-remission therapy
Follow-up visits following post-remission therapy

Collaborators and Investigators

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

Sponsor

Antisoma Research

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

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, 2007

Primary Completion (Anticipated)

June 1, 2010

Study Registration Dates

First Submitted

July 14, 2008

First Submitted That Met QC Criteria

July 14, 2008

First Posted (Estimate)

July 15, 2008

Study Record Updates

Last Update Posted (Estimate)

October 13, 2010

Last Update Submitted That Met QC Criteria

October 12, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 509912

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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