Secondary Acute Myeloid Leukemia (Secondary AML, sAML) Clinical Trial
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
| Verified date | October 2010 |
| Source | Antisoma Research |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 420 |
| Est. completion date | |
| Est. primary completion date | June 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Hospital Italiano de La Plata | Buenos Aires | |
| Argentina | Clinical Hematology Service | Ciudad Autónoma de Bs. As. | |
| Argentina | Hospital General de Agudos "Dr. Teodoro Alvarez" | Ciudad Autónoma de Bs. As. | |
| Argentina | Hospital Provincial de Cordoba | Cordoba | |
| Argentina | Sanatorio Parque | Rosario - Santa Fe | |
| Australia | Royal Adelaide Hospital | Adelaide | South Australia |
| Australia | Box Hill Hospital | Box Hill | Victoria |
| Australia | The Canberra Hospital | Garran | Australian Capital Territory |
| Australia | Peter MacCallum Cancer Centre | Melbourne | Victoria |
| Australia | The Alfred Hospital | Melbourne | Victoria |
| Australia | Royal Perth Hospital | Perth | Western Australia |
| Australia | Royal North Shore Hospital | St Leonards | New South Wales |
| Australia | Westmead Hospital | Westmead | New South Wales |
| Austria | LKH-Universitats Klinikum Graz | Graz | |
| Austria | Landeskrankenhaus Salzburg | Salzburg | |
| Austria | Landesklinikum St. Polten | St. Polten | |
| Belgium | Algemeen Ziekenhuis Sint-Jan | Brugge | |
| Belgium | Institut Jules Bordet | Brussels | |
| Belgium | University Hospital Gent | Gent | |
| Belgium | UCL de Mont-Godinne | Yvoir | |
| Canada | QEII Center for Clinical Research | Halifax | |
| Canada | London Health Sciences Centre | London | Ontario |
| Canada | The Ottawa Hospital - General Campus | Ottawa | |
| Chile | Hospital DIPRECA | Santiago | |
| Chile | Hospital Santa Maria | Santiago | |
| Chile | Hospital Dr. Gustavo Fricke | Viña del Mar | |
| Czech Republic | General University Hospital Prague | Prague | |
| Czech Republic | Institute of Haematology and Blood Transfusion Prague | Prague | |
| Czech Republic | University Hospital Kralovske Vinohrady Prague | Prague | |
| Ecuador | Instituto Ecuatoriano de Seguridad Social Hospital Regional Teodoro Maldonado Carbó | Guayaquil | |
| Ecuador | Hospital Carlos Andrade Marin | Quito | |
| Ecuador | Hospital Militar | Quito | |
| Estonia | North Estonia Medical Centre Foundation | Tallinn | |
| France | Hopital Sud | Amiens | |
| France | Hopital Edouard Herriot | Lyon | |
| France | Hopital-DIEU | Paris | |
| France | Hopital du Haut Leveque | Pessac | |
| France | Hopital Bretonneau - CHRU de Tours | Tours | |
| France | Hopital de Versailles | Versailles | Le Cheaney |
| Germany | Campus Virchow Klinikum | Berlin | |
| Germany | Charite - Campus Benjamin Franklin | Berlin | |
| Germany | Evangelische Kliniken GmbH | Bonn | |
| Germany | St Antonius Hospital | Eschweiler | |
| Germany | Universitatsklinikum Essen | Essen | |
| Germany | Stadtische Kliniken Frankfurt | Frankfurt | |
| Germany | Asklepios Kliniken Altona | Hamburg | |
| Germany | Medizin Hochschule Hannover | Hannover | |
| Germany | Universitätsklinikum Schleswig-Holstein | Kiel | |
| Germany | Klinikum Leverkusen | Leverkusen | |
| Germany | Markische Kliniken GmbH Klinikim Ludenscheid | Lüdenscheid | |
| Germany | Universitätsmedizin Mannheim | Mannheim | |
| Hungary | Szent Istvan and Szent Laszlo Corporate Hospital - Out-patient Clinic of the Municipality Government | Budapest | |
| Hungary | Petz Aladar County Teaching Hospital | Gyor | |
| Hungary | Kaposi Mór County Teaching Hospital | Kaposvár | |
| Hungary | University of Pecs | Pecs | |
| Israel | Rambam Medical Center | Haifa | |
| Israel | Hadassah Medical Center | Jerusalem | |
| Israel | Chaim Sheba Medical Center | Tel Hashomer | |
| Italy | University of Brescia | Brescia | |
| Italy | A.O.U Careggi | Firenze | |
| Italy | A.O.U San Martino | Genova | |
| Italy | A.O. Cardarelli | Napoli | |
| Italy | A.O. San Salvatore | Pesaro | |
| Italy | A.O.U Pisana Santa Chiara | Pisa | |
| Italy | Università degli Studi di Roma "La Sapienza" | Roma | |
| Italy | Ospedale S. Eugenio | Rome | |
| Italy | Istituto Clinico Humanitas | Rozzano | |
| Korea, Republic of | Inje University Busan Paik Hospital | Busan | |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Ewha Womans University Mokdong Hospital | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | Severance Hospital in YUHS | Seoul | |
| Korea, Republic of | Ajou University Hospital | Suwon | |
| Poland | Teaching Hospital of the Medical University in Bialystok | Bialystok | |
| Poland | Academic Clinical Centre - Teaching Hospital of the Medical University of Gdansk | Gdansk | |
| Poland | Nicolaus Copernicus Provincial Specialist Hospital in Lodz | Lodz | |
| Poland | Provincial Hospital in Opole | Opole | |
| Poland | Poznan Stare Miasto Health Care Facility | Poznan | |
| Poland | Janusz Korczak Provincial Specialist Hospital | Slupsk | |
| Poland | Institute of Hematology and Transfusiology | Warsaw | |
| Poland | Military Institue of Health Services | Warsaw | |
| Poland | Independent Public University Hospital No. 1 in Wroclaw | Wroclaw | |
| Romania | Dr. Constantin Opris County Emergency Hospital, Internal Medicine Department | Baia Mare | |
| Romania | Brasov County Emergency Clinical Hospital | Brasov | |
| Romania | Colentina Clinical Hospital, Internal Medicine Department | Bucharest | |
| Romania | Coltea Clinical Hospital | Bucharest | |
| Romania | Fundeni Clinical Institute "Stefan Berceanu" Center for Hematology and Bone Marrow Transplant | Bucharest | |
| Romania | Sibiu County Clinical Hospital, Internal Clinic II | Sibiu | |
| Russian Federation | Municipal Medical Institution Municipal Hospital #1 | Cherepovets | |
| Russian Federation | State Medical Institution Sverdlovsk Regional Clinical Hospital #1 | Ekaterinburg | |
| Russian Federation | State Medical Institution Irkutsk Regional Clinical Hospital | Irkutsk | |
| Russian Federation | State Medical Institution Territorial Clinical Hospital #1 | Khabarovsk | |
| Russian Federation | State Medical Institution Territorial Clinical Oncological Center | Krasnodar | |
| Russian Federation | Moscow State Medical Institution Municipal | Moscow | |
| Russian Federation | State Institution Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences | Moscow | |
| Russian Federation | Municipal Medical Institution | Perm | |
| Russian Federation | State Medical Institution Republican Hospital n.a. V.A. Baranov | Petrozavodsk | Republic of Karelia |
| Russian Federation | State Higher Educational Instution Rostov State | Rostow Am Don | |
| Russian Federation | Federal Center of Heart, Blood and Endocrinology | St. Petersburg | |
| Russian Federation | 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 | State Medical Institution Leningrad Regional Clinical Hospital | St. Petersburg | |
| Spain | Hospital Germans Trias i Pujol | Badalona | |
| Spain | Hospital Clinic I Provinicial | Barcelona | |
| Spain | Hospital de la Santa Creu I Sant Pau | Barcelona | |
| Spain | Hospital Del Mar | Barcelona | |
| Spain | Hospital Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario La Fe | Valencia | |
| Taiwan | Changhua Christian Hospital (CCH) | Changhua | |
| Taiwan | Chang Gung Memorial Hospital Kao Hsiung Branch | Niao-Sung Hsiang | Kaohsiung Hsien |
| Taiwan | Chinese Medical University Hospital (CMUH) | Taichung City | |
| Taiwan | National Cheng Kung University Hospital (NCKUH) | Tainan | |
| Taiwan | Mackay Memorial Hospital | Taipei | |
| Taiwan | National Taiwan University Hospital (NTUH) | Taipei | |
| Taiwan | Veterans General Hospital Taipei (VGH-TP) | Taipei | |
| Ukraine | Public Institution 'Cherkasy Regional Oncology Center' | Cherkasy | |
| Ukraine | Dnipropetrovsk City General Clinical Hospital #4 | Dnipropetrovsk | |
| Ukraine | Ivano-Frankivsk State Medical University | Ivano-Frankivsk | |
| Ukraine | Khmelnytsky Regional Hospital | Khmelnytsky | |
| Ukraine | State Institution 'Institute of Blood Pathology and Transfusion Medicine under the UAMS' | Lviv | |
| Ukraine | Mykolaiv Regional Clinical Hospital | Mykolaiv | |
| Ukraine | Odesa Regional Clinical Hospital | Odesa | |
| Ukraine | Ukrainian Medical Academy of Dentistry | Poltava | |
| Ukraine | M.I. Pyrohov Vinnytsya Regional Clinical Hospital | Vinnytsya | |
| Ukraine | O.F. Herbachevsky Zhytomyr Regional Clinical Hospital | Zhytomyr | |
| United Kingdom | University Hospital of Wales | Cardiff | Wales |
| United Kingdom | King's College Hospital | London | |
| United Kingdom | Churchill Hospital | Oxford | |
| United States | University of Michigan Cancer Center | Ann Arbor | Michigan |
| United States | The Blood and Marrow Transplant Group of GA | Atlanta | Georgia |
| United States | Winship Cancer Institute, Emory University | Atlanta | Georgia |
| United States | University of Colorado Health Sciences Center | Aurora | Colorado |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | Northwestern University School of Medicine | Chicago | Illinois |
| United States | Rush University Medical Center | Chicago | Illinois |
| United States | Taussig Cancer Center, Cleveland Clinic | Cleveland | Ohio |
| United States | Rocky Mountain Blood and Marrow Transplant Program | Denver | Colorado |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Cancer Center of the Carolinas | Greenville | South Carolina |
| United States | Penn State Hershey Medical Center | Hershey | Pennsylvania |
| United States | University of Iowa Hospitals | Iowa City | Iowa |
| United States | Northshore Hospital - Monter Cancer Center | Lake Success | New York |
| United States | Michigan State University | Lansing | Michigan |
| United States | UCLA Medical Center | Los Angelas | California |
| United States | Univ of Southern California Comprehensive Cancer Center | Los Angeles | California |
| United States | James Graham Brown Cancer Center | Louisville | Kentucky |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
| United States | Western Pennsylvania Hospital | Pittsburgh | Pennsylvania |
| United States | Oregon Health & Science University | Portland | Oregon |
| United States | Roger Williams Medical Center | Providence | Rhode Island |
| United States | Intermountain Healthcare | Salt Lake City | Utah |
| United States | University of California San Francisco | San Francisco | California |
| United States | LSU Health Sciences Center, Feist-Weiller Cancer Center | Shreveport | Louisiana |
| United States | Wake Forest University Health Sciences | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Antisoma Research |
United States, Argentina, Australia, Austria, Belgium, Canada, Chile, Czech Republic, Ecuador, Estonia, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Poland, Romania, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | No | |
| Secondary | Median duration of remission and median duration of disease free survival. | Follow-up visits following post-remission therapy | No |