Clinical trial NCT00715637: Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Secondary Acute Myeloid Leukemia (Secondary AML, sAML)
Keywords: AML
Leukemia
MDS
Amonafide
Cytarabine
Daunorubicin
Lymphatic disorders
Lead sponsor: Antisoma Research
Sponsor class: INDUSTRY
First posted: 2008-07-15
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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