Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study
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
1 other identifier
interventional
420
21 countries
149
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
149 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2007
CompletedFirst Submitted
Initial submission to the registry
July 14, 2008
CompletedFirst Posted
Study publicly available on registry
July 15, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2010
CompletedOctober 13, 2010
October 1, 2010
3 years
July 14, 2008
October 12, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Median duration of remission and median duration of disease free survival.
Follow-up visits following post-remission therapy
Study Arms (2)
Arm A
EXPERIMENTALAmonafide in Combination with Cytarabine
Arm B
ACTIVE COMPARATORDaunorubicin in Combination with Cytarabine
Interventions
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)
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)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (158)
UCLA Medical Center
Los Angelas, California, 90095, United States
Univ of Southern California Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California San Francisco
San Francisco, California, 94143, United States
University of Colorado Health Sciences Center
Aurora, Colorado, 80045, United States
Rocky Mountain Blood and Marrow Transplant Program
Denver, Colorado, 80218, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
The Blood and Marrow Transplant Group of GA
Atlanta, Georgia, 30342, United States
Northwestern University School of Medicine
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Iowa Hospitals
Iowa City, Iowa, 52242, United States
James Graham Brown Cancer Center
Louisville, Kentucky, 40202, United States
LSU Health Sciences Center, Feist-Weiller Cancer Center
Shreveport, Louisiana, 71103, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02114, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109, United States
Michigan State University
Lansing, Michigan, 48910, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Northshore Hospital - Monter Cancer Center
Lake Success, New York, 11042, United States
Duke University Medical Center
Durham, North Carolina, 27707, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Taussig Cancer Center, Cleveland Clinic
Cleveland, Ohio, 44195, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17036, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224, United States
Roger Williams Medical Center
Providence, Rhode Island, 02908, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Cancer Center of the Carolinas
Greenville, South Carolina, 29605, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Intermountain Healthcare
Salt Lake City, Utah, 84103, United States
Hospital Italiano de La Plata
Buenos Aires, B1900AXI, Argentina
Hospital General de Agudos "Dr. Teodoro Alvarez"
Ciudad Autónoma de Bs. As., C1406FWY, Argentina
Clinical Hematology Service
Ciudad Autónoma de Bs. As., C1437JCP, Argentina
Hospital Provincial de Cordoba
Córdoba, Argentina
Sanatorio Parque
Rosario - Santa Fe, S2000DSU, Argentina
The Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3002, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Royal Perth Hospital
Perth, Western Australia, 6000, Australia
LKH-Universitats Klinikum Graz
Graz, 8036, Austria
Landeskrankenhaus Salzburg
Salzburg, 5020, Austria
Landesklinikum St. Polten
Sankt Pölten, 3100, Austria
University Hospital Gent
Ghent, Gent, 9000, Belgium
Algemeen Ziekenhuis Sint-Jan
Bruges, 8000, Belgium
Institut Jules Bordet
Brussels, 1000, Belgium
UCL de Mont-Godinne
Yvoir, 5530, Belgium
London Health Sciences Centre
London, Ontario, N6A 4L6, Canada
QEII Center for Clinical Research
Halifax, B3H 2Y9, Canada
The Ottawa Hospital - General Campus
Ottawa, K1H 8L6, Canada
Hospital Santa Maria
Santiago, 7530204, Chile
Hospital DIPRECA
Santiago, 7571831, Chile
Hospital Dr. Gustavo Fricke
Viña del Mar, 2570017, Chile
University Hospital Kralovske Vinohrady Prague
Prague, 100 34, Czechia
General University Hospital Prague
Prague, 128 08, Czechia
Institute of Haematology and Blood Transfusion Prague
Prague, Czechia
Instituto Ecuatoriano de Seguridad Social Hospital Regional Teodoro Maldonado Carbó
Guayaquil, Ecuador
Hospital Carlos Andrade Marin
Quito, Ecuador
Hospital Militar
Quito, Ecuador
North Estonia Medical Centre Foundation
Tallinn, 13419, Estonia
Hopital de Versailles
Versailles, Le Cheaney, 78150, France
Hopital Sud
Amiens, 80054, France
Hopital Edouard Herriot
Lyon, 69437, France
Hopital-DIEU
Paris, 75004, France
Hopital du Haut Leveque
Pessac, 33604, France
Hopital Bretonneau - CHRU de Tours
Tours, 37044, France
Charite - Campus Benjamin Franklin
Berlin, 12200, Germany
Campus Virchow Klinikum
Berlin, 13353, Germany
Evangelische Kliniken GmbH
Bonn, 53113, Germany
St Antonius Hospital
Eschweiler, 52249, Germany
Universitatsklinikum Essen
Essen, 45122, Germany
Stadtische Kliniken Frankfurt
Frankfurt, 65929, Germany
Asklepios Kliniken Altona
Hamburg, 22763, Germany
Medizin Hochschule Hannover
Hanover, 30625, Germany
Universitätsklinikum Schleswig-Holstein
Kiel, 24116, Germany
Klinikum Leverkusen
Leverkusen, 51375, Germany
Markische Kliniken GmbH Klinikim Ludenscheid
Lüdenscheid, 58515, Germany
Universitätsmedizin Mannheim
Mannheim, D-68167, Germany
Szent Istvan and Szent Laszlo Corporate Hospital - Out-patient Clinic of the Municipality Government
Budapest, 1097, Hungary
Petz Aladar County Teaching Hospital
Győr, 9024, Hungary
Kaposi Mór County Teaching Hospital
Kaposvár, 7400, Hungary
University of Pecs
Pécs, Hungary
Rambam Medical Center
Haifa, 31096, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Chaim Sheba Medical Center
Tel Litwinsky, 52621, Israel
University of Brescia
Brescia, 25123, Italy
A.O.U Careggi
Florence, 50134, Italy
A.O.U San Martino
Genova, 16132, Italy
A.O. Cardarelli
Napoli, 80131, Italy
A.O. San Salvatore
Pesaro, 61100, Italy
A.O.U Pisana Santa Chiara
Pisa, 56125, Italy
Università degli Studi di Roma "La Sapienza"
Roma, 00161, Italy
Ospedale S. Eugenio
Rome, 00144, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
Teaching Hospital of the Medical University in Bialystok
Bialystok, 15-276, Poland
Academic Clinical Centre - Teaching Hospital of the Medical University of Gdansk
Gdansk, 80-952, Poland
Nicolaus Copernicus Provincial Specialist Hospital in Lodz
Lodz, 93-513, Poland
Provincial Hospital in Opole
Opole, 45-372, Poland
Poznan Stare Miasto Health Care Facility
Poznan, 61-833, Poland
Janusz Korczak Provincial Specialist Hospital
Słupsk, 76-200, Poland
Military Institue of Health Services
Warsaw, 00-909, Poland
Institute of Hematology and Transfusiology
Warsaw, 02-776, Poland
Independent Public University Hospital No. 1 in Wroclaw
Wroclaw, 50-369, Poland
Dr. Constantin Opris County Emergency Hospital, Internal Medicine Department
Baia Mare, 430031, Romania
Brasov County Emergency Clinical Hospital
Brasov, 500236, Romania
Colentina Clinical Hospital, Internal Medicine Department
Bucharest, 020125, Romania
Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant
Bucharest, 022328, Romania
Coltea Clinical Hospital
Bucharest, 030171, Romania
Sibiu County Clinical Hospital, Internal Clinic II
Sibiu, 550245, Romania
State Medical Institution Republican Hospital n.a. V.A. Baranov
Petrozavodsk, Republic of Karelia, 185014, Russia
Municipal Medical Institution Municipal Hospital #1
Cherepovets, 162627, Russia
State Medical Institution Irkutsk Regional Clinical Hospital
Irkutsk, 664079, Russia
State Medical Institution Territorial Clinical Hospital #1
Khabarovsk, 680009, Russia
State Medical Institution Territorial Clinical Oncological Center
Krasnodar, 350040, Russia
State Institution Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences
Moscow, 115478, Russia
Moscow State Medical Institution Municipal
Moscow, 125101, Russia
Municipal Medical Institution
Perm, 614010, Russia
State Higher Educational Instution Rostov State
Rostov-on-Don, Russia
State Medical Institution Leningrad Regional Clinical Hospital
Saint Petersburg, 194291, Russia
State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
Saint Petersburg, 197101, Russia
Federal Center of Heart, Blood and Endocrinology
Saint Petersburg, Russia
State Medical Institution Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, 620102, Russia
Inje University Busan Paik Hospital
Busan, 614-735, South Korea
Seoul National University Hospital
Seoul, 110-799, South Korea
Severance Hospital in YUHS
Seoul, 120-752, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Ewha Womans University Mokdong Hospital
Seoul, 158-710, South Korea
Ajou University Hospital
Suwon, 443-721, South Korea
Hospital Germans Trias i Pujol
Badalona, 08916, Spain
Hospital Del Mar
Barcelona, 08003, Spain
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic I Provinicial
Barcelona, 08036, Spain
Hospital de la Santa Creu I Sant Pau
Barcelona, 08041, Spain
Hospital Universitario La Fe
Valencia, Spain
Chang Gung Memorial Hospital Kao Hsiung Branch
Niao-Sung Hsiang, Kaohsiung Hsien, 83301, Taiwan
Changhua Christian Hospital (CCH)
Changhua, 500, Taiwan
Chinese Medical University Hospital (CMUH)
Taichung, 404, Taiwan
National Cheng Kung University Hospital (NCKUH)
Tainan, 704, Taiwan
National Taiwan University Hospital (NTUH)
Taipei, 100, Taiwan
Mackay Memorial Hospital
Taipei, 104, Taiwan
Veterans General Hospital Taipei (VGH-TP)
Taipei, 112, Taiwan
Public Institution 'Cherkasy Regional Oncology Center'
Cherkasy, 18009, Ukraine
Dnipropetrovsk City General Clinical Hospital #4
Dnipropetrovsk, 49102, Ukraine
Ivano-Frankivsk State Medical University
Ivano-Frankivsk, 76018, Ukraine
Khmelnytsky Regional Hospital
Khmelnytsky, 29000, Ukraine
State Institution 'Institute of Blood Pathology and Transfusion Medicine under the UAMS'
Lviv, 79044, Ukraine
Mykolaiv Regional Clinical Hospital
Mykolaiv, 54058, Ukraine
Odesa Regional Clinical Hospital
Odesa, 65025, Ukraine
Ukrainian Medical Academy of Dentistry
Poltava, Ukraine
M.I. Pyrohov Vinnytsya Regional Clinical Hospital
Vinnytsia, 21018, Ukraine
O.F. Herbachevsky Zhytomyr Regional Clinical Hospital
Zhytomyr, 10013, Ukraine
University Hospital of Wales
Cardiff, Wales, CF14 4XW, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
Churchill Hospital
Oxford, OX3 9DLJ, United Kingdom
Related Publications (2)
Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. doi: 10.1200/JCO.2014.57.0952. Epub 2015 Mar 2.
PMID: 25732165DERIVEDLindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, Damon LE, Powell BL, Lindeman N, Steensma DP, Wadleigh M, DeAngelo DJ, Neuberg D, Stone RM, Ebert BL. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015 Feb 26;125(9):1367-76. doi: 10.1182/blood-2014-11-610543. Epub 2014 Dec 30.
PMID: 25550361DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
July 14, 2008
First Posted
July 15, 2008
Study Start
June 1, 2007
Primary Completion
June 1, 2010
Last Updated
October 13, 2010
Record last verified: 2010-10