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

NCT ID: NCT01191801

Last Updated: 2018-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 711 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-17
• Study Completion Date: 2017-03-01

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

vosaroxin + cytarabine

Intervention Type: DRUG

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)

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

Group Type: PLACEBO_COMPARATOR

placebo + cytarabine

Intervention Type: DRUG

Placebo days 1 and 4: volume matched to vosaroxin

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

Interventions

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)

Intervention Type: DRUG

placebo + cytarabine

Placebo days 1 and 4: volume matched to vosaroxin

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

Intervention Type: DRUG

Other Intervention Names

control

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunesis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda Neuman, MD

Role: STUDY_DIRECTOR

Sunesis Pharmaceuticals

Locations

Moores UCSD Cancer Center

La Jolla, California, United States

UCLA Division of Hematology/Oncology

Los Angeles, California, United States

Sharp Clinical Oncology Research

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

HCA HealthONE - Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, United States

George Washington University-Medical Faculty Associates

Washington D.C., District of Columbia, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Baptist Cancer Institute

Jacksonville, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Georgia Health Sciences University

Augusta, Georgia, United States

Rush University Medical Center, Division of Hematology/Oncology

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, 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

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Ellis Fischel Cancer Center, University of Missouri Health Care

Columbia, Missouri, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

North Shore Long Island Jewish Health System

Lake Success, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

New York Medical College, Division of Oncology/Hematology

Valhalla, New York, United States

Mecklenburg Medical Group

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

University Hospitals fo Cleveland

Cleveland, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Family Cancer Center

Memphis, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia

Houston, Texas, United States

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Department of Medicine Section of Hematology/Oncology, West Virginia University Hospitals, Mary Babb Randolph Cancer Center, West Virginia University

Morgantown, West Virginia, United States

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Haematology Department, Gosford Hospital

Gosford, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Andrew Love Cancer Center, Geelong Hospital, Barwon Health

Geelong, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Department of Clinical Haematology and BMT Service, Royal Melbourne Hospital

Parkville, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Universitatsklinik Graz, Universitatsklinik fur Innere Medizin, Abteilung fur Hamatologie

Graz, , Austria

University Hospital for Internal Medicine V, Innsbruck Medical University

Innsbruck, , Austria

Landeskrankenhaus Salzburg, Universitaetsklinik fur innere Medizin lll, Universitaetsklinikum der PMU

Salzburg, , Austria

AKH Wien / MedUniWien Universtatsklinik fur Innere Medizin 1

Vienna, , Austria

ZNA Middleheim Lindendreef 1

Antwerp, , Belgium

ZNA Stuivenberg, Lange Beeldekensstraat 267

Antwerp, , Belgium

AZ St.-Jan Brugge-Oostende AV

Bruges, , Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

UZ Leuven, campus Gasthuisberg, Department of Haematology

Leuven, , Belgium

H.-Hartziekenhuis Roeselare - Menen vzw

Roeselare, , Belgium

Division of Hematology, Vancouver General Hospital

Vancouver, British Columbia, Canada

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

University Health Network, Princess Margaret Hospital

Toronto, Ontario, Canada

Charles LeMoyne Hospital

Greenfield Park, Quebec, Canada

Fakultni nemocnice Kralovske Vinohrady, Oddeleni klinicke hematologie

Prague, Srobarova, Czechia

Fakultni nemocnice Brno, Interni hematoonkologicka klinika

Brno, , Czechia

Fakultni nemocnice Hradec Kralove, 2. Interni klinika-oddeleni klinicke hematologie

Hradec Králové, , Czechia

CHU Lille, Service des maladies du sang, Hopital Huriez

Lille, Lille Cedex, France

CHU Angers, Service des maladies du sang

Angers, , France

Hopital Avicenne- Departement Onco-hematologie

Bobigny, , France

Hopital Mignot

Le Chesnay, , France

Institut Paoli Calmettes

Marseille, , France

CHU Nantes Hotel Dieu, Service d'hematologie clinique

Nantes, , 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-Bénite, , France

Service d'hematologie- Hopital Purpan- CHU de Toulouse

Toulouse, , France

St. Johannes-Hospital

Duisburg, , Germany

Klinikum Frankfurt am Main-Hochst, Department of Hematology and Oncology, Klinikum Frankfurt Academic Hospital of the University of Frankfurt

Frankfurt, , Germany

Universitatsklinikum Hamburg-Eppendorf; ll. Medizinische Klinik und Poliklinik; Onkologie, Hamatologie und Knochenmarktransplantation

Hamburg, , Germany

Medizinische Hochschule Hannover, Abteilung Hamatologie

Hanover, , Germany

SLK-Kliniken Heilbronn GmbH, Medizinische Klinik

Heilbronn, , Germany

Staedtisches Krankenhaus Kiel GmbH, Infektionsambulanz der 2. Medizinischen Klinik

Kiel, , Germany

Klinikum St. Georg gGmbH; Klinik fur Internistische Onkologie/Hamatologie

Leipzig, , Germany

Klinikum rechts der Isar der Technischen Universitat Munchen lll, Medizinische Klinik

Munich, , Germany

University Hospital of Muenster

Münster, , Germany

University of Debrecen Medical and Health Sciences Center

Debrecen, , Hungary

Petz Aladar County Hospital

Győr, , Hungary

kaposi Mor Oktato Korhaz Belgyogyaszati Osztaly

Kaposvár, , Hungary

Szegedi Tudomanyegyetem, 11. Belgyogyaszati Klinika

Szeged, , Hungary

Ospedale "A. Perrino", U.O. Compessa di Ematologia

Brindisi, , Italy

Azienda Ospedaliero-Universitaria Sant'Anna, Sezione di Ematologia, Dipartmento di Science Biomediche e Terapie Avanzate

Ferrara, , Italy

Ospedaliera Universitaria San Martino di Genova

Genova, , Italy

Ospedale "Vito Fazzi", U.O Ematologia

Lecce, , Italy

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

Haematology Research, Auckland District Health Board, Auckland City Hospital

Grafton, Auckland, New Zealand

Canterbury Health Laboratories

Christchurch, , New Zealand

Department of Haematology, Waikato Hospital

Hamilton, , New Zealand

Regional Cancer Treatment Service, Palmerston North Hospital

Palmerston North, , New Zealand

Uniwersyteckle Centrum Kliniczne

Gdansk, , Poland

Klinika Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego, Szpital Kliniczny Przemiemienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, , Poland

Seoul National University Hospital

Seoul, , South Korea

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, , South Korea

Seoul St. Mary's Hospital

Seoul, , South Korea

Dept. of Hematology, Asan Medical Center

Seoul, , South Korea

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Centro Oncologico MD Anderson International Espana

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Sont Llatzer

Palma de Mallorca, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitari Politecnic la Fe Hematology Department

Valencia, , Spain

Blackpool Victoria Hospital, Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, , United Kingdom

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

Cambridge, , United Kingdom

Department of Haematology, University Hospital of Wales

Cardiff, , United Kingdom

Queen's Centre for Oncology and Hematology, Castle Hill Hospital

Cottingham, , United Kingdom

Leicester Royal Infirmary, University Hospitals of Leicester, NHS Trust

Leicester, , United Kingdom

Department of Haematology, Royal Liverpool University Hospital

Liverpool, , United Kingdom

Department of Haematology, Guy's Hospital

London, , United Kingdom

Central Manchester University Hospitals NHS Trust, Manchester Royal Infirmary

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Czechia; France; Germany; Hungary; Italy; New Zealand; Poland; South Korea; Spain; United Kingdom

References

Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, Strickland SA, Schiller GJ, Jabbour E, Erba HP, Pigneux A, Horst HA, Recher C, Klimek VM, Cortes J, Roboz GJ, Odenike O, Thomas X, Havelange V, Maertens J, Derigs HG, Heuser M, Damon L, Powell BL, Gaidano G, Carella AM, Wei A, Hogge D, Craig AR, Fox JA, Ward R, Smith JA, Acton G, Mehta C, Stuart RK, Kantarjian HM. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015 Sep;16(9):1025-1036. doi: 10.1016/S1470-2045(15)00201-6. Epub 2015 Jul 30.

Reference Type: DERIVED

PMID: 26234174 (View on PubMed)

Other Identifiers

2010-021961-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VOS-AML-301

Identifier Type: -

Identifier Source: org_study_id