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

NCT ID: NCT00715637

Last Updated: 2010-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Secondary Acute Myeloid Leukemia (Secondary AML, sAML)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm A

Amonafide in Combination with Cytarabine

Group Type EXPERIMENTAL

Amonafide and Cytarabine

Intervention Type DRUG

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)

Arm B

Daunorubicin in Combination with Cytarabine

Group Type ACTIVE_COMPARATOR

Daunorubicin and Cytarabine

Intervention Type DRUG

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)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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)

Intervention Type 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)

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Antisoma Research

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Antisoma

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Istituto Clinico Humanitas

Rozzano, , Italy

Site Status

UCLA Medical Center

Los Angelas, California, United States

Site Status

Univ of Southern California Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Site Status

Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, United States

Site Status

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

The Blood and Marrow Transplant Group of GA

Atlanta, Georgia, United States

Site Status

Northwestern University School of Medicine

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals

Iowa City, Iowa, United States

Site Status

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

LSU Health Sciences Center, Feist-Weiller Cancer Center

Shreveport, Louisiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status

Michigan State University

Lansing, Michigan, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Northshore Hospital - Monter Cancer Center

Lake Success, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Taussig Cancer Center, Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Roger Williams Medical Center

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Cancer Center of the Carolinas

Greenville, South Carolina, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Intermountain Healthcare

Salt Lake City, Utah, United States

Site Status

Hospital Italiano de La Plata

Buenos Aires, , Argentina

Site Status

Hospital General de Agudos "Dr. Teodoro Alvarez"

Ciudad Autónoma de Bs. As., , Argentina

Site Status

Clinical Hematology Service

Ciudad Autónoma de Bs. As., , Argentina

Site Status

Hospital Provincial de Cordoba

Córdoba, , Argentina

Site Status

Sanatorio Parque

Rosario - Santa Fe, , Argentina

Site Status

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

LKH-Universitats Klinikum Graz

Graz, , Austria

Site Status

Landeskrankenhaus Salzburg

Salzburg, , Austria

Site Status

Landesklinikum St. Polten

Sankt Pölten, , Austria

Site Status

University Hospital Gent

Ghent, Gent, Belgium

Site Status

Algemeen Ziekenhuis Sint-Jan

Bruges, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

UCL de Mont-Godinne

Yvoir, , Belgium

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

QEII Center for Clinical Research

Halifax, , Canada

Site Status

The Ottawa Hospital - General Campus

Ottawa, , Canada

Site Status

Hospital Santa Maria

Santiago, , Chile

Site Status

Hospital DIPRECA

Santiago, , Chile

Site Status

Hospital Dr. Gustavo Fricke

Viña del Mar, , Chile

Site Status

University Hospital Kralovske Vinohrady Prague

Prague, , Czechia

Site Status

General University Hospital Prague

Prague, , Czechia

Site Status

Institute of Haematology and Blood Transfusion Prague

Prague, , Czechia

Site Status

Instituto Ecuatoriano de Seguridad Social Hospital Regional Teodoro Maldonado Carbó

Guayaquil, , Ecuador

Site Status

Hospital Carlos Andrade Marin

Quito, , Ecuador

Site Status

Hospital Militar

Quito, , Ecuador

Site Status

North Estonia Medical Centre Foundation

Tallinn, , Estonia

Site Status

Hopital de Versailles

Versailles, Le Cheaney, France

Site Status

Hopital Sud

Amiens, , France

Site Status

Hopital Edouard Herriot

Lyon, , France

Site Status

Hopital-DIEU

Paris, , France

Site Status

Hopital du Haut Leveque

Pessac, , France

Site Status

Hopital Bretonneau - CHRU de Tours

Tours, , France

Site Status

Charite - Campus Benjamin Franklin

Berlin, , Germany

Site Status

Campus Virchow Klinikum

Berlin, , Germany

Site Status

Evangelische Kliniken GmbH

Bonn, , Germany

Site Status

St Antonius Hospital

Eschweiler, , Germany

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

Stadtische Kliniken Frankfurt

Frankfurt, , Germany

Site Status

Asklepios Kliniken Altona

Hamburg, , Germany

Site Status

Medizin Hochschule Hannover

Hanover, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Site Status

Klinikum Leverkusen

Leverkusen, , Germany

Site Status

Markische Kliniken GmbH Klinikim Ludenscheid

Lüdenscheid, , Germany

Site Status

Universitätsmedizin Mannheim

Mannheim, , Germany

Site Status

Szent Istvan and Szent Laszlo Corporate Hospital - Out-patient Clinic of the Municipality Government

Budapest, , Hungary

Site Status

Petz Aladar County Teaching Hospital

Győr, , Hungary

Site Status

Kaposi Mór County Teaching Hospital

Kaposvár, , Hungary

Site Status

University of Pecs

Pécs, , Hungary

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

University of Brescia

Brescia, , Italy

Site Status

A.O.U Careggi

Florence, , Italy

Site Status

A.O.U San Martino

Genova, , Italy

Site Status

A.O. Cardarelli

Napoli, , Italy

Site Status

A.O. San Salvatore

Pesaro, , Italy

Site Status

A.O.U Pisana Santa Chiara

Pisa, , Italy

Site Status

Università degli Studi di Roma "La Sapienza"

Roma, , Italy

Site Status

Ospedale S. Eugenio

Rome, , Italy

Site Status

Teaching Hospital of the Medical University in Bialystok

Bialystok, , Poland

Site Status

Academic Clinical Centre - Teaching Hospital of the Medical University of Gdansk

Gdansk, , Poland

Site Status

Nicolaus Copernicus Provincial Specialist Hospital in Lodz

Lodz, , Poland

Site Status

Provincial Hospital in Opole

Opole, , Poland

Site Status

Poznan Stare Miasto Health Care Facility

Poznan, , Poland

Site Status

Janusz Korczak Provincial Specialist Hospital

Słupsk, , Poland

Site Status

Military Institue of Health Services

Warsaw, , Poland

Site Status

Institute of Hematology and Transfusiology

Warsaw, , Poland

Site Status

Independent Public University Hospital No. 1 in Wroclaw

Wroclaw, , Poland

Site Status

Dr. Constantin Opris County Emergency Hospital, Internal Medicine Department

Baia Mare, , Romania

Site Status

Brasov County Emergency Clinical Hospital

Brasov, , Romania

Site Status

Colentina Clinical Hospital, Internal Medicine Department

Bucharest, , Romania

Site Status

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

Bucharest, , Romania

Site Status

Coltea Clinical Hospital

Bucharest, , Romania

Site Status

Sibiu County Clinical Hospital, Internal Clinic II

Sibiu, , Romania

Site Status

State Medical Institution Republican Hospital n.a. V.A. Baranov

Petrozavodsk, Republic of Karelia, Russia

Site Status

Municipal Medical Institution Municipal Hospital #1

Cherepovets, , Russia

Site Status

State Medical Institution Irkutsk Regional Clinical Hospital

Irkutsk, , Russia

Site Status

State Medical Institution Territorial Clinical Hospital #1

Khabarovsk, , Russia

Site Status

State Medical Institution Territorial Clinical Oncological Center

Krasnodar, , Russia

Site Status

State Institution Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences

Moscow, , Russia

Site Status

Moscow State Medical Institution Municipal

Moscow, , Russia

Site Status

Municipal Medical Institution

Perm, , Russia

Site Status

State Higher Educational Instution Rostov State

Rostov-on-Don, , Russia

Site Status

State Medical Institution Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

Site Status

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, , Russia

Site Status

Federal Center of Heart, Blood and Endocrinology

Saint Petersburg, , Russia

Site Status

State Medical Institution Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Site Status

Inje University Busan Paik Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital in YUHS

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Ewha Womans University Mokdong Hospital

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Del Mar

Barcelona, , Spain

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic I Provinicial

Barcelona, , Spain

Site Status

Hospital de la Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Chang Gung Memorial Hospital Kao Hsiung Branch

Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan

Site Status

Changhua Christian Hospital (CCH)

Changhua, , Taiwan

Site Status

Chinese Medical University Hospital (CMUH)

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital (NCKUH)

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital (NTUH)

Taipei, , Taiwan

Site Status

Mackay Memorial Hospital

Taipei, , Taiwan

Site Status

Veterans General Hospital Taipei (VGH-TP)

Taipei, , Taiwan

Site Status

Public Institution 'Cherkasy Regional Oncology Center'

Cherkasy, , Ukraine

Site Status

Dnipropetrovsk City General Clinical Hospital #4

Dnipropetrovsk, , Ukraine

Site Status

Ivano-Frankivsk State Medical University

Ivano-Frankivsk, , Ukraine

Site Status

Khmelnytsky Regional Hospital

Khmelnytsky, , Ukraine

Site Status

State Institution 'Institute of Blood Pathology and Transfusion Medicine under the UAMS'

Lviv, , Ukraine

Site Status

Mykolaiv Regional Clinical Hospital

Mykolaiv, , Ukraine

Site Status

Odesa Regional Clinical Hospital

Odesa, , Ukraine

Site Status

Ukrainian Medical Academy of Dentistry

Poltava, , Ukraine

Site Status

M.I. Pyrohov Vinnytsya Regional Clinical Hospital

Vinnytsia, , Ukraine

Site Status

O.F. Herbachevsky Zhytomyr Regional Clinical Hospital

Zhytomyr, , Ukraine

Site Status

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Austria Belgium Canada Chile Czechia Ecuador Estonia France Germany Hungary Israel Italy Poland Romania Russia South Korea Spain Taiwan Ukraine United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 25732165 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25550361 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

509912

Identifier Type: -

Identifier Source: org_study_id

NCT00509912

Identifier Type: -

Identifier Source: nct_alias