Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study
- Conditions
- Secondary Acute Myeloid Leukemia (Secondary AML, sAML)
- Interventions
- Registration Number
- NCT00715637
- Lead Sponsor
- Antisoma Research
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 420
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B Daunorubicin and Cytarabine Daunorubicin in Combination with Cytarabine Arm A Amonafide and Cytarabine Amonafide in Combination with Cytarabine
- Primary Outcome Measures
Name Time Method 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. Course 1/Course 2 Day 37 bone marrow assessments and confirmation bone marrow 30 days later
- Secondary Outcome Measures
Name Time Method Median duration of remission and median duration of disease free survival. Follow-up visits following post-remission therapy
Trial Locations
- Locations (158)
Univ of Southern California Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Taussig Cancer Center, Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
The Blood and Marrow Transplant Group of GA
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
LSU Health Sciences Center, Feist-Weiller Cancer Center
🇺🇸Shreveport, Louisiana, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Hospital Italiano de La Plata
🇦🇷Buenos Aires, Argentina
Algemeen Ziekenhuis Sint-Jan
🇧🇪Brugge, Belgium
Hospital Dr. Gustavo Fricke
🇨🇱Viña del Mar, Chile
Hospital Militar
🇪🇨Quito, Ecuador
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Sanatorio Parque
🇦🇷Rosario - Santa Fe, Argentina
Landesklinikum St. Polten
🇦🇹St. Polten, Austria
University Hospital Kralovske Vinohrady Prague
🇨🇿Prague, Czech Republic
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
The Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hospital General de Agudos "Dr. Teodoro Alvarez"
🇦🇷Ciudad Autónoma de Bs. As., Argentina
University Hospital Gent
🇧🇪Gent, Belgium
UCL de Mont-Godinne
🇧🇪Yvoir, Belgium
Hospital Santa Maria
🇨🇱Santiago, Chile
General University Hospital Prague
🇨🇿Prague, Czech Republic
Provincial Hospital in Opole
🇵🇱Opole, Poland
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
National Cheng Kung University Hospital (NCKUH)
🇨🇳Tainan, Taiwan
Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine
Cancer Center of the Carolinas
🇺🇸Greenville, South Carolina, United States
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
Kaposi Mór County Teaching Hospital
ðŸ‡ðŸ‡ºKaposvár, Hungary
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Teaching Hospital of the Medical University in Bialystok
🇵🇱Bialystok, Poland
Colentina Clinical Hospital, Internal Medicine Department
🇷🇴Bucharest, Romania
Sibiu County Clinical Hospital, Internal Clinic II
🇷🇴Sibiu, Romania
Chinese Medical University Hospital (CMUH)
🇨🇳Taichung City, Taiwan
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Institut Jules Bordet
🇧🇪Brussels, Belgium
Hospital DIPRECA
🇨🇱Santiago, Chile
University of Pecs
ðŸ‡ðŸ‡ºPecs, Hungary
Nicolaus Copernicus Provincial Specialist Hospital in Lodz
🇵🇱Lodz, Poland
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Szent Istvan and Szent Laszlo Corporate Hospital - Out-patient Clinic of the Municipality Government
ðŸ‡ðŸ‡ºBudapest, Hungary
Academic Clinical Centre - Teaching Hospital of the Medical University of Gdansk
🇵🇱Gdansk, Poland
Poznan Stare Miasto Health Care Facility
🇵🇱Poznan, Poland
Military Institue of Health Services
🇵🇱Warsaw, Poland
Institute of Hematology and Transfusiology
🇵🇱Warsaw, Poland
Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant
🇷🇴Bucharest, Romania
State Medical Institution Republican Hospital n.a. V.A. Baranov
🇷🇺Petrozavodsk, Republic of Karelia, Russian Federation
State Medical Institution Irkutsk Regional Clinical Hospital
🇷🇺Irkutsk, Russian Federation
State Medical Institution Territorial Clinical Oncological Center
🇷🇺Krasnodar, Russian Federation
M.I. Pyrohov Vinnytsya Regional Clinical Hospital
🇺🇦Vinnytsya, Ukraine
Veterans General Hospital Taipei (VGH-TP)
🇨🇳Taipei, Taiwan
Brasov County Emergency Clinical Hospital
🇷🇴Brasov, Romania
State Medical Institution Leningrad Regional Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
Federal Center of Heart, Blood and Endocrinology
🇷🇺St. Petersburg, Russian Federation
Changhua Christian Hospital (CCH)
🇨🇳Changhua, Taiwan
Public Institution 'Cherkasy Regional Oncology Center'
🇺🇦Cherkasy, Ukraine
Ivano-Frankivsk State Medical University
🇺🇦Ivano-Frankivsk, Ukraine
State Institution 'Institute of Blood Pathology and Transfusion Medicine under the UAMS'
🇺🇦Lviv, Ukraine
National Taiwan University Hospital (NTUH)
🇨🇳Taipei, Taiwan
Municipal Medical Institution Municipal Hospital #1
🇷🇺Cherepovets, Russian Federation
Mykolaiv Regional Clinical Hospital
🇺🇦Mykolaiv, Ukraine
Ukrainian Medical Academy of Dentistry
🇺🇦Poltava, Ukraine
O.F. Herbachevsky Zhytomyr Regional Clinical Hospital
🇺🇦Zhytomyr, Ukraine
University of California San Francisco
🇺🇸San Francisco, California, United States
Rocky Mountain Blood and Marrow Transplant Program
🇺🇸Denver, Colorado, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Intermountain Healthcare
🇺🇸Salt Lake City, Utah, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Universitätsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Northwestern University School of Medicine
🇺🇸Chicago, Illinois, United States
Ospedale S. Eugenio
🇮🇹Rome, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Ajou University Hospital
🇰🇷Suwon, Korea, Republic of
Severance Hospital in YUHS
🇰🇷Seoul, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
State Medical Institution Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
State Medical Institution Territorial Clinical Hospital #1
🇷🇺Khabarovsk, Russian Federation
Rambam Medical Center
🇮🇱Haifa, Israel
University of Brescia
🇮🇹Brescia, Italy
A.O.U Careggi
🇮🇹Firenze, Italy
Universitätsmedizin Mannheim
🇩🇪Mannheim, Germany
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Università degli Studi di Roma "La Sapienza"
🇮🇹Roma, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Petz Aladar County Teaching Hospital
ðŸ‡ðŸ‡ºGyÅ‘r, Hungary
Khmelnytsky Regional Hospital
🇺🇦Khmelnytsky, Ukraine
A.O.U San Martino
🇮🇹Genova, Italy
A.O. Cardarelli
🇮🇹Napoli, Italy
A.O.U Pisana Santa Chiara
🇮🇹Pisa, Italy
A.O. San Salvatore
🇮🇹Pesaro, Italy
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital de la Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Churchill Hospital
🇬🇧Oxford, United Kingdom
Janusz Korczak Provincial Specialist Hospital
🇵🇱Slupsk, Poland
Independent Public University Hospital No. 1 in Wroclaw
🇵🇱Wroclaw, Poland
Dr. Constantin Opris County Emergency Hospital, Internal Medicine Department
🇷🇴Baia Mare, Romania
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Moscow State Medical Institution Municipal
🇷🇺Moscow, Russian Federation
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic I Provinicial
🇪🇸Barcelona, Spain
Municipal Medical Institution
🇷🇺Perm, Russian Federation
Chang Gung Memorial Hospital Kao Hsiung Branch
🇨🇳Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan
State Institution Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences
🇷🇺Moscow, Russian Federation
Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
State Higher Educational Instution Rostov State
🇷🇺Rostow Am Don, Russian Federation
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals
🇺🇸Iowa City, Iowa, United States
UCLA Medical Center
🇺🇸Los Angelas, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northshore Hospital - Monter Cancer Center
🇺🇸Lake Success, New York, United States
Michigan State University
🇺🇸Lansing, Michigan, United States
Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Roger Williams Medical Center
🇺🇸Providence, Rhode Island, United States
Clinical Hematology Service
🇦🇷Ciudad Autónoma de Bs. As., Argentina
Hospital Provincial de Cordoba
🇦🇷Cordoba, Argentina
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
LKH-Universitats Klinikum Graz
🇦🇹Graz, Austria
QEII Center for Clinical Research
🇨🇦Halifax, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Charite - Campus Benjamin Franklin
🇩🇪Berlin, Germany
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Canada
Institute of Haematology and Blood Transfusion Prague
🇨🇿Prague, Czech Republic
Hospital Carlos Andrade Marin
🇪🇨Quito, Ecuador
Hopital Sud
🇫🇷Amiens, France
North Estonia Medical Centre Foundation
🇪🇪Tallinn, Estonia
Instituto Ecuatoriano de Seguridad Social Hospital Regional Teodoro Maldonado Carbó
🇪🇨Guayaquil, Ecuador
Hopital-DIEU
🇫🇷Paris, France
Hopital de Versailles
🇫🇷Versailles, Le Cheaney, France
Hopital Edouard Herriot
🇫🇷Lyon, France
Hopital du Haut Leveque
🇫🇷Pessac, France
Hopital Bretonneau - CHRU de Tours
🇫🇷Tours, France
St Antonius Hospital
🇩🇪Eschweiler, Germany
Asklepios Kliniken Altona
🇩🇪Hamburg, Germany
Evangelische Kliniken GmbH
🇩🇪Bonn, Germany
Campus Virchow Klinikum
🇩🇪Berlin, Germany
Stadtische Kliniken Frankfurt
🇩🇪Frankfurt, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Medizin Hochschule Hannover
🇩🇪Hannover, Germany
Klinikum Leverkusen
🇩🇪Leverkusen, Germany
Markische Kliniken GmbH Klinikim Ludenscheid
🇩🇪Lüdenscheid, Germany
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Dnipropetrovsk City General Clinical Hospital #4
🇺🇦Dnipropetrovsk, Ukraine
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
University of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States