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Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML (VALOR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunesis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01191801
First received: August 27, 2010
Last updated: March 29, 2017
Last verified: March 2017
  Purpose
This study compared treatment groups of patients treated with vosaroxin and cytarabine versus patients treated with placebo and cytarabine.

Condition Intervention Phase
Acute Myeloid Leukemia Drug: vosaroxin + cytarabine Drug: placebo + cytarabine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Controlled, Double-Blind, Multinational Clinical Study of the Efficacy and Safety of Vosaroxin and Cytarabine Versus Placebo and Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (VALOR)

Resource links provided by NLM:


Further study details as provided by Sunesis Pharmaceuticals:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Up to 5 years or duration of study ]
    Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival


Secondary Outcome Measures:
  • Complete Remission (CR) Rate Based on Modified International Working Group (IWG) Criteria. [ Time Frame: 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.

  • All Cause Mortality [ Time Frame: 30 Days ]
    Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality

  • All Cause Mortality [ Time Frame: 60 Days ]
    Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality


Other Outcome Measures:
  • Overall Remission (OR) Rate Based on the IWG Response Criteria [ Time Frame: Up to 5 years or the duration of the study ]

    Group A patient OR compared to Group B patient OR

    Overall Remission includes Complete Remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with incomplete blood count recovery (CRi), and Partial Remission (PR). Complete remission means bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts as typically defined by the IWG. Both CRi and CRp refer complete remission but with incomplete blood count and platelet recovery, respectively. PR, or partial remission, refers to remission in which bone marrow contains blast counts between 5 and 25 percent.


  • Event Free Survival (EFS) [ Time Frame: Up to 5 years or duration of study ]
  • Leukemia-Free Survival (LFS) [ Time Frame: Up to 5 years or the duration of the study ]
    Durability of remission (CR) assessed by LFS


Enrollment: 711
Study Start Date: December 17, 2010
Study Completion Date: March 1, 2017
Primary Completion Date: September 26, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: 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
Drug: vosaroxin + cytarabine

Vosaroxin days 1 and 4: 90 mg/m2 for induction 1; 70 mg/m2 for all other cycles

Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

Placebo Comparator: Group B: 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
Drug: placebo + cytarabine

Placebo days 1 and 4: volume matched to vosaroxin

Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

Other Name: control

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191801

  Hide Study Locations
Locations
United States, California
Moores UCSD Cancer Center
La Jolla, California, United States, 92093
UCLA Division of Hematology/Oncology
Los Angeles, California, United States, 90095
Sharp Clinical Oncology Research
San Diego, California, United States, 92123
University of California San Francisco
San Francisco, California, United States, 94143
United States, Colorado
HCA HealthONE - Rocky Mountain Blood and Marrow Transplant Program
Denver, Colorado, United States, 80218
United States, District of Columbia
George Washington University-Medical Faculty Associates
Washington, District of Columbia, United States, 20037
United States, Florida
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
United States, Illinois
Rush University Medical Center, Division of Hematology/Oncology
Chicago, Illinois, United States, 60612
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
St. Francis Medical Group Oncology and Hematology Specialists
Indianapolis, Indiana, United States, 46237
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Ellis Fischel Cancer Center, University of Missouri Health Care
Columbia, Missouri, United States, 65203
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
North Shore Long Island Jewish Health System
Lake Success, New York, United States, 11042
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 100065
Weill Cornell Medical College
New York, New York, United States, 10065
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
New York Medical College, Division of Oncology/Hematology
Valhalla, New York, United States, 10595
United States, North Carolina
Mecklenburg Medical Group
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals fo Cleveland
Cleveland, Ohio, United States, 44106
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Family Cancer Center
Memphis, Tennessee, United States, 38119
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia
Houston, Texas, United States, 77030
Cancer Care Centers of South Texas
San Antonio, Texas, United States, 78229
United States, West Virginia
Department of Medicine Section of Hematology/Oncology, West Virginia University Hospitals, Mary Babb Randolph Cancer Center, West Virginia University
Morgantown, West Virginia, United States, 26506
Australia, Australian Capital Territory
The Canberra Hospital
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Concord Repatriation General Hospital
Concord, New South Wales, Australia, 2139
Haematology Department, Gosford Hospital
Gosford, New South Wales, Australia, 2250
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Brisbane, Queensland, Australia, 4029
Australia, South Australia
Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Andrew Love Cancer Center, Geelong Hospital, Barwon Health
Geelong, Victoria, Australia, 3220
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Department of Clinical Haematology and BMT Service, Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Austria
Universitatsklinik Graz, Universitatsklinik fur Innere Medizin, Abteilung fur Hamatologie
Graz, Austria, 8036
University Hospital for Internal Medicine V, Innsbruck Medical University
Innsbruck, Austria, 6020
Landeskrankenhaus Salzburg, Universitaetsklinik fur innere Medizin lll, Universitaetsklinikum der PMU
Salzburg, Austria, 5020
AKH Wien / MedUniWien Universtatsklinik fur Innere Medizin 1
Wien, Austria, 1090
Belgium
ZNA Middleheim Lindendreef 1
Antwerpen, Belgium, 2020
ZNA Stuivenberg, Lange Beeldekensstraat 267
Antwerpen, Belgium
AZ St.-Jan Brugge-Oostende AV
Brugge, Belgium, 8000
Cliniques Universitaires Saint Luc
Brussels, Belgium, 1200
UZ Leuven, campus Gasthuisberg, Department of Haematology
Leuven, Belgium, B 3000
H.-Hartziekenhuis Roeselare - Menen vzw
Roeselare, Belgium, 8800
Canada, British Columbia
Division of Hematology, Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, New Brunswick
Saint John Regional Hospital
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
University Health Network, Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Charles LeMoyne Hospital
Greenfield Park, Quebec, Canada, J4V 2H1
Czech Republic
Fakultni nemocnice Kralovske Vinohrady, Oddeleni klinicke hematologie
Praha, Srobarova, Czech Republic, 100 34 Praha 10
Fakultni nemocnice Brno, Interni hematoonkologicka klinika
Brno, Czech Republic, 625 00
Fakultni nemocnice Hradec Kralove, 2. Interni klinika-oddeleni klinicke hematologie
Hradec Kralove, Czech Republic, 500 05
France
CHU Lille, Service des maladies du sang, Hopital Huriez
Lille, Lille Cedex, France, 59037
CHU Angers, Service des maladies du sang
Angers Cedex 01, France, 49033
Hopital Avicenne- Departement Onco-hematologie
Bobigny, France, 93000
Hopital Mignot
Le Chesnay, France, 78157
Institut Paoli Calmettes
Marseille, France, 13009
CHU Nantes Hotel Dieu, Service d'hematologie clinique
Nantes, France, 44093
CHU de Bordeaux- Hopital Haut-Leveque, Centre Francois Magendle
Pessac, France, 33604
Centre Hospitalier Lyon Sud - Service d'Hematologie - Pavillon Marcel Berard - Bat. 1G - 1er etage, 165 Chemin du grand Revoyet
Pierre Benite, France, 69495
Service d'hematologie- Hopital Purpan- CHU de Toulouse
Toulouse, France, 31059
Germany
St. Johannes-Hospital
Duisburg, Germany, 47166
Klinikum Frankfurt am Main-Hochst, Department of Hematology and Oncology, Klinikum Frankfurt Academic Hospital of the University of Frankfurt
Frankfurt, Germany, 65929
Universitatsklinikum Hamburg-Eppendorf; ll. Medizinische Klinik und Poliklinik; Onkologie, Hamatologie und Knochenmarktransplantation
Hamburg, Germany, 20246
Medizinische Hochschule Hannover, Abteilung Hamatologie
Hannover, Germany, 30625
SLK-Kliniken Heilbronn GmbH, Medizinische Klinik
Heilbronn, Germany, 74078
Staedtisches Krankenhaus Kiel GmbH, Infektionsambulanz der 2. Medizinischen Klinik
Kiel, Germany, 24116
Klinikum St. Georg gGmbH; Klinik fur Internistische Onkologie/Hamatologie
Leipzig, Germany, 04129
University Hospital of Muenster
Muenster, Germany, 48149
Klinikum rechts der Isar der Technischen Universitat Munchen lll, Medizinische Klinik
Munich, Germany, 81675
Hungary
University of Debrecen Medical and Health Sciences Center
Debrecen, Hungary, H-4030
Petz Aladar County Hospital
Gyor, Hungary, H-9024
kaposi Mor Oktato Korhaz Belgyogyaszati Osztaly
Kaposvar, Hungary, H-7400
Szegedi Tudomanyegyetem, 11. Belgyogyaszati Klinika
Szeged, Hungary, H-6720
Italy
Ospedale "A. Perrino", U.O. Compessa di Ematologia
Brindisi, Italy, 72100
Azienda Ospedaliero-Universitaria Sant'Anna, Sezione di Ematologia, Dipartmento di Science Biomediche e Terapie Avanzate
Ferrara, Italy, 44121
Ospedaliera Universitaria San Martino di Genova
Genova, Italy, 16132
Ospedale "Vito Fazzi", U.O Ematologia
Lecce, Italy, 73100
AORN "A. Cardarelli", U.O.S.C. Ematologia con TMO
Napoli, Italy, 80131
Azienda Ospedaliero-Universitaria Maggiore Della Carita, Struttura Complessa Direzione Universitaria Ematologia
Novara, Italy, 28100
Fondazione IRCCS, Policlinico S. Matteo - Dipartimento di Ematologia
Pavia, Italy, 27100
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Seoul, Korea, Republic of, 135-710
Seoul St. Mary's Hospital
Seoul, Korea, Republic of, 137-701
Dept. of Hematology, Asan Medical Center
Seoul, Korea, Republic of, 138-736
New Zealand
Haematology Research, Auckland District Health Board, Auckland City Hospital
Grafton, Auckland, New Zealand, 1023
Canterbury Health Laboratories
Christchurch, New Zealand, 8011
Department of Haematology, Waikato Hospital
Hamilton, New Zealand, 3240
Regional Cancer Treatment Service, Palmerston North Hospital
Palmerston North, New Zealand, 4414
Poland
Uniwersyteckle Centrum Kliniczne
Gdansk, Poland, 80-952
Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego, Szpital Kliniczny Przemiemienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan, Poland, 60-569
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw, Poland, 50-369
Spain
Hospital Universitari Germans Trias i Pujol
Badalona (Barcelona), Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital del Mar
Barcelona, Spain
Centro Oncologico MD Anderson International Espana
Madrid, Spain, 28033
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Sont Llatzer
Palma de Mallorca, Spain, 07198
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitari Politecnic la Fe Hematology Department
Valencia, Spain, 46026
United Kingdom
Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust
Blackpool, United Kingdom, FY3 8NR
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Department of Haematology, University Hospital of Wales
Cardiff, United Kingdom, CF14 4XW
Queen's Centre for Oncology and Hematology, Castle Hill Hospital
Cottingham, United Kingdom, GY16 5JQ
Leicester Royal Infirmary, University Hospitals of Leicester, NHS Trust
Leicester, United Kingdom, LE1 5WW
Department of Haematology, Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP
Department of Haematology, Guy's Hospital
London, United Kingdom, SE1 9RT
Central Manchester University Hospitals NHS Trust, Manchester Royal Infirmary
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Sunesis Pharmaceuticals
Investigators
Study Director: Linda Neuman, MD Sunesis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sunesis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01191801     History of Changes
Other Study ID Numbers: VOS-AML-301
2010-021961-61 ( EudraCT Number )
Study First Received: August 27, 2010
Results First Received: April 12, 2016
Last Updated: March 29, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data of individual participants experiencing Serious Adverse Events

Keywords provided by Sunesis Pharmaceuticals:
Leukemia
Acute Myeloid Leukemia
Hematologic
Hematologic diseases
Blood
Cancer
Malignancy
Vosaroxin
Cytarabine
First Relapsed AML
Refractory AML
VALOR
Sunesis
Voreloxin
SNS-595

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 19, 2017