Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT01191801
- Lead Sponsor
- Sunesis Pharmaceuticals
- Brief Summary
This study compared treatment groups of patients treated with vosaroxin and cytarabine versus patients treated with placebo and cytarabine.
- Detailed Description
The study includes additional objectives to ones listed above as Outcome Measures. These additional objectives also compared treatment groups in the following:
CR + CRp rate, defined as CR + CRp based on modified IWG response criteria.
Combined CR rate (CR+CRp+CRi).
Percentage of patients who have post-treatment (subsequent) transplantation.
Percentage of patients who received subsequent non-protocol therapy (including transplantation).
Safety and tolerability.
In keeping with FDA guidance for adaptive trial designs, the study incorporated an independent DSMB (Drug Safety Monitoring Board) to address potential uncertainty concerning the true treatment affect between the treatment groups and to address a deterioration of power from a small difference. Sunesis remained blinded and had no involvement in the interim data analysis, interpretation, or adaptive design. Based on the results of the interim data analysis the DSMB recommended an increase in the target number of deaths from 375 in 450 patients to 562 in 675 patients which based on a 5% dropout rate increased enrollment from 475 to 712.
The primary analysis was performed when the target number of deaths had been achieved based on a permuted block randomization procedure, stratified by disease status (refractory, first relapse with duration of first CR or CRp ≥ 90 days and \< 12 months, or first relapse with duration of first CR or CRp ≥ 12 months and ≤ 24 months), age (\< 60 years or ≥ 60 years), and geographic location (US or outside US). The study included periods of screening, treatment / hematologic recovery, post-treatment follow-up, and long-term follow-up for survival.
Follow-up was monthly during the first year, every 2 months during the second year, and every 3 months thereafter until death, withdrawal of consent, or loss to follow-up, whichever occurred first. Long-term follow-up began for all patients when the required number of deaths for primary analysis had been met; thereafter, survival data were collected every 4 months until death, withdrawal of consent, or loss to follow-up, whichever occurred first.
The long term follow-up for this study continues at this time and the September 2014 date reflects database lock for primary analyses reflected in the Results Section. During long term follow-up Sunesis is not collecting Adverse Events.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 711
- Provided signed, written informed consent
- At least 18 years of age
- Had a diagnosis of AML according to World Health Organization (WHO) classification
- First relapsed or refractory AML (refractory to initial induction therapy) with at least 5% blasts by bone marrow or aspirate or 1% blasts in peripheral blood with additional requirements for relapsed or refractory
- Had an ECOG score of 0-2
- Had adequate liver and renal function as indicated by certain laboratory values
- Had adequate cardiac function (left ventricular ejection fraction at least 40% by multiple gated acquisition scan or ECG)
- Nonfertile or agreed to use an adequate method of contraception until 30 days after the last treatment
- Had any clinically significant nonhematologic toxicity after prior chemotherapy recovered to Grade 1 per NCI-CTCAE
- Had acute promyelocytic leukemia
- Had more than 2 cycles of induction therapy for AML
- Had completed a single cycle of treatment containing a total dose of 5 g/m2 or more of cytarabine within 90 days before randomization
- Refractory to or relapsed within the previous 3 months after therapy with an IDAC- or HIDAC-containing regimen
- Had received a hematopoietic stem cell transplant (HSCT) within the previous 90 days
- Had received active immunosuppressive therapy for graft-versus-host disease (GVHD) within 2 weeks before study start
- Had any other severe concurrent disease, or have a history of serious disease involving the heart, kidney, liver, or other organ system
- Had evidence of central nervous system involvement of active AML
- Had other active malignancies (including other hematologic malignancies) or been diagnosed with other malignancies within the last 12 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
- Had an active, uncontrolled infection
- Had received any other investigational therapy within 14 days or not recovered from acute affects of the other investigational therapy
- Had received prior or current hydroxyurea or medications to reduce blast count within 24 hours before randomization
- Had received previous treatment with vosaroxin
- Pregnant or lactating
- Had any other medical, psychological, or social condition that may interfere with consent, study participation, or follow-up
- Had known HIV seropositivity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: vosaroxin + cytarabine vosaroxin + cytarabine vosaroxin (short IV infusion within 10 minutes) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation Group B: placebo + cytarabine placebo + cytarabine placebo (short IV infusion within 10 minutes and volume matched to vosaroxin) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation
- Primary Outcome Measures
Name Time Method Overall Survival Up to 5 years or duration of study Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival
- Secondary Outcome Measures
Name Time Method All Cause Mortality 60 Days Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality
Complete Remission (CR) Rate Based on Modified International Working Group (IWG) Criteria. Up to 5 years or duration of study Group A (Vosaroxin + cytarabine) patient CR as compared to Group B (placebo + cytarabine) patient CR. Complete remission (CR) is typically defined using IWG criteria as bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts.
Trial Locations
- Locations (124)
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Department of Clinical Haematology and BMT Service, Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Landeskrankenhaus Salzburg, Universitaetsklinik fur innere Medizin lll, Universitaetsklinikum der PMU
🇦🇹Salzburg, Austria
AKH Wien / MedUniWien Universtatsklinik fur Innere Medizin 1
🇦🇹Wien, Austria
Charles LeMoyne Hospital
🇨🇦Greenfield Park, Quebec, Canada
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
New York Medical College, Division of Oncology/Hematology
🇺🇸Valhalla, New York, United States
UT Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Saint John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Debrecen Medical and Health Sciences Center
🇭🇺Debrecen, Hungary
Department of Medicine Section of Hematology/Oncology, West Virginia University Hospitals, Mary Babb Randolph Cancer Center, West Virginia University
🇺🇸Morgantown, West Virginia, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Family Cancer Center
🇺🇸Memphis, Tennessee, United States
Sharp Clinical Oncology Research
🇺🇸San Diego, California, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
St. Francis Medical Group Oncology and Hematology Specialists
🇺🇸Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
Rush University Medical Center, Division of Hematology/Oncology
🇺🇸Chicago, Illinois, United States
North Shore Long Island Jewish Health System
🇺🇸Lake Success, New York, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Haematology Department, Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
The Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
ZNA Stuivenberg, Lange Beeldekensstraat 267
🇧🇪Antwerpen, Belgium
University Hospital for Internal Medicine V, Innsbruck Medical University
🇦🇹Innsbruck, Austria
Fakultni nemocnice Kralovske Vinohrady, Oddeleni klinicke hematologie
🇨🇿Praha, Srobarova, Czechia
Institut Paoli Calmettes
🇫🇷Marseille, France
Service d'hematologie- Hopital Purpan- CHU de Toulouse
🇫🇷Toulouse, France
Universitatsklinikum Hamburg-Eppendorf; ll. Medizinische Klinik und Poliklinik; Onkologie, Hamatologie und Knochenmarktransplantation
🇩🇪Hamburg, Germany
SLK-Kliniken Heilbronn GmbH, Medizinische Klinik
🇩🇪Heilbronn, Germany
Klinikum rechts der Isar der Technischen Universitat Munchen lll, Medizinische Klinik
🇩🇪Munich, Germany
Ospedale "A. Perrino", U.O. Compessa di Ematologia
🇮🇹Brindisi, Italy
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
🇰🇷Seoul, Korea, Republic of
Haematology Research, Auckland District Health Board, Auckland City Hospital
🇳🇿Grafton, Auckland, New Zealand
Canterbury Health Laboratories
🇳🇿Christchurch, New Zealand
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
🇵🇱Wroclaw, Poland
Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego, Szpital Kliniczny Przemiemienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Uniwersyteckle Centrum Kliniczne
🇵🇱Gdansk, Poland
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Department of Haematology, University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Department of Haematology, Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom
Department of Haematology, Guy's Hospital
🇬🇧London, United Kingdom
Azienda Ospedaliero-Universitaria Sant'Anna, Sezione di Ematologia, Dipartmento di Science Biomediche e Terapie Avanzate
🇮🇹Ferrara, Italy
University of California San Francisco
🇺🇸San Francisco, California, United States
HCA HealthONE - Rocky Mountain Blood and Marrow Transplant Program
🇺🇸Denver, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Hospital Sont Llatzer
🇪🇸Palma de Mallorca, Spain
Hospital Universitari Politecnic la Fe Hematology Department
🇪🇸Valencia, Spain
Georgia Health Sciences University
🇺🇸Augusta, Georgia, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Ellis Fischel Cancer Center, University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
CHU Angers, Service des maladies du sang
🇫🇷Angers Cedex 01, France
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Fakultni nemocnice Hradec Kralove, 2. Interni klinika-oddeleni klinicke hematologie
🇨🇿Hradec Kralove, Czechia
UCLA Division of Hematology/Oncology
🇺🇸Los Angeles, California, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University Hospitals fo Cleveland
🇺🇸Cleveland, Ohio, United States
The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia
🇺🇸Houston, Texas, United States
George Washington University-Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Mecklenburg Medical Group
🇺🇸Charlotte, North Carolina, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
St. Johannes-Hospital
🇩🇪Duisburg, Germany
ZNA Middleheim Lindendreef 1
🇧🇪Antwerpen, Belgium
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Petz Aladar County Hospital
🇭🇺Gyor, Hungary
Ospedaliera Universitaria San Martino di Genova
🇮🇹Genova, Italy
Hopital Avicenne- Departement Onco-hematologie
🇫🇷Bobigny, France
Central Manchester University Hospitals NHS Trust, Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Division of Hematology, Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Universitatsklinik Graz, Universitatsklinik fur Innere Medizin, Abteilung fur Hamatologie
🇦🇹Graz, Austria
AZ St.-Jan Brugge-Oostende AV
🇧🇪Brugge, Belgium
UZ Leuven, campus Gasthuisberg, Department of Haematology
🇧🇪Leuven, Belgium
H.-Hartziekenhuis Roeselare - Menen vzw
🇧🇪Roeselare, Belgium
Hopital Mignot
🇫🇷Le Chesnay, France
CHU Nantes Hotel Dieu, Service d'hematologie clinique
🇫🇷Nantes, France
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Klinikum St. Georg gGmbH; Klinik fur Internistische Onkologie/Hamatologie
🇩🇪Leipzig, Germany
Andrew Love Cancer Center, Geelong Hospital, Barwon Health
🇦🇺Geelong, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
University Hospital of Muenster
🇩🇪Muenster, Germany
CHU Lille, Service des maladies du sang, Hopital Huriez
🇫🇷Lille, Lille Cedex, France
CHU de Bordeaux- Hopital Haut-Leveque, Centre Francois Magendle
🇫🇷Pessac, France
Centre Hospitalier Lyon Sud - Service d'Hematologie - Pavillon Marcel Berard - Bat. 1G - 1er etage, 165 Chemin du grand Revoyet
🇫🇷Pierre Benite, France
Dept. of Hematology, Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Medizinische Hochschule Hannover, Abteilung Hamatologie
🇩🇪Hannover, Germany
Klinikum Frankfurt am Main-Hochst, Department of Hematology and Oncology, Klinikum Frankfurt Academic Hospital of the University of Frankfurt
🇩🇪Frankfurt, Germany
Fakultni nemocnice Brno, Interni hematoonkologicka klinika
🇨🇿Brno, Czechia
kaposi Mor Oktato Korhaz Belgyogyaszati Osztaly
🇭🇺Kaposvar, Hungary
Staedtisches Krankenhaus Kiel GmbH, Infektionsambulanz der 2. Medizinischen Klinik
🇩🇪Kiel, Germany
Szegedi Tudomanyegyetem, 11. Belgyogyaszati Klinika
🇭🇺Szeged, Hungary
Ospedale "Vito Fazzi", U.O Ematologia
🇮🇹Lecce, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
AORN "A. Cardarelli", U.O.S.C. Ematologia con TMO
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria Maggiore Della Carita, Struttura Complessa Direzione Universitaria Ematologia
🇮🇹Novara, Italy
Fondazione IRCCS, Policlinico S. Matteo - Dipartimento di Ematologia
🇮🇹Pavia, Italy
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Leicester Royal Infirmary, University Hospitals of Leicester, NHS Trust
🇬🇧Leicester, United Kingdom
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Regional Cancer Treatment Service, Palmerston North Hospital
🇳🇿Palmerston North, New Zealand
Centro Oncologico MD Anderson International Espana
🇪🇸Madrid, Spain
Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust
🇬🇧Blackpool, United Kingdom
Queen's Centre for Oncology and Hematology, Castle Hill Hospital
🇬🇧Cottingham, United Kingdom
Department of Haematology, Waikato Hospital
🇳🇿Hamilton, New Zealand
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada