Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT02785900
- Lead Sponsor
- Seagen Inc.
- Brief Summary
The purpose of this study in AML patients is to test whether vadastuximab talirine (SGN-CD33A; 33A) combined with either azacitidine or decitabine improves remission rates and extends overall survival as compared to placebo combined with either azacitidine or decitabine.
- Detailed Description
Hypomethylating agents (HMAs), such as decitabine or azacitidine, are considered a standard treatment for older patients with AML. The primary goals of this study are to test whether patients treated with an HMA (either decitabine or azacitidine) in combination with 33A will have better anti-tumor activity and/or survive longer than patients treated with an HMA in combination with placebo.
Patients who meet eligibility criteria will be randomly assigned to one of two treatment groups: 1) 33A plus HMA (Experimental Arm); or 2) placebo plus HMA (Comparator Arm). In addition to evaluating survival and remission rates, the minimal residual disease (MRD)-negative remission rate, duration of remission, event free- and leukemia-free survival, and safety and tolerability will be compared between arms.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 240
- Newly diagnosed, previously untreated, cytologically/histologically confirmed de novo or secondary AML according to World Health Organization (WHO) classification (except for acute promyelocytic leukemia (APL))
- Intermediate or adverse cytogenetic risk
- Eligible for therapy with either decitabine or azacitidine
- Acceptable hematologic and organ function
- AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or t(15;17)
- Patients who are candidates for allogeneic stem cell transplant at the time of enrollment
- Patients with a history of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis
- Received prior treatment with HMA or chemotherapy for antecedent myelodysplastic syndrome (MDS)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 33A + HMA 33A 33A plus azacitidine or decitabine 33A + HMA decitabine 33A plus azacitidine or decitabine placebo + HMA placebo placebo plus azacitidine or decitabine 33A + HMA azacitidine 33A plus azacitidine or decitabine placebo + HMA azacitidine placebo plus azacitidine or decitabine placebo + HMA decitabine placebo plus azacitidine or decitabine
- Primary Outcome Measures
Name Time Method Overall Survival Up to 1.5 years Time from randomization to death due to any cause
Composite Complete Remission (CRc) Rate Up to 1.5 years Number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) according to the modified response criteria for acute myeloid leukemia (AML) per Cheson 2003.
- Secondary Outcome Measures
Name Time Method Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate Up to 1.5 years Number of patients who achieve both remission (CR or CRi) and MRD-negative status
Event-free Survival Up to approximately 11.24 months Event-free survival is calculated from the time of randomization to the first documentation of progression, relapse, or death, whichever comes first. Patients who do not have event (progression, relapse, or death) prior to analysis cutoff date are censored at the date of last response assessment. Patients who started another anticancer therapy before progression, relapse, or death are censored at the date of last response assessment prior to the start of new therapy. Patients who do not have response assessment post-baseline are censored at the date of randomization.
Duration of Remission Up to approximately 9.5 months Duration of remission is calculated from the first documentation of CR or CRi to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.
Leukemia-free Survival Up to approximately 9.49 months Leukemia-free survival is calculated from the first documentation of blast clearance (CR, CRi, mLFS) to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.
Incidence of Grade 3 or Higher Laboratory Abnormalities Up to 1.5 years Participants who experienced a laboratory grade increase to Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\], v4.03)
Time to Complete Remission Up to 1.5 years Time to CR or CRi is the time from randomization to the first documentation of CR/CRi
Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events Up to 1.5 years Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. SAE = serious adverse event. "Study treatment" in this data set refers to blinded study treatment.
Mortality Rates at Day 30 and Day 60 Up to 60 days 30- and 60-day survival from date of randomization. Estimated using Kaplan-Meier method.
Trial Locations
- Locations (128)
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
LSU Health Sciences Center / Feist Weiller Cancer Center
🇺🇸Shreveport, Louisiana, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Florida Cancer Specialists - South Region
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - North Region
🇺🇸Saint Petersburg, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Intermountain Blood and Marrow Transplant/Acute Leukemia Program
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Semmelweis Egyetem
🇭🇺Budapest, Hungary
LKH Salzburg, Universitatsklinikum der PMU
🇦🇹Salzburg, Austria
CHRU de Lille
🇫🇷Lille cedex, France
Centre Hospitalier Universitaire Sart Tilman Liege
🇧🇪Liege, Belgium
Saint Francis Hospital / Bon Secours
🇺🇸Greenville, South Carolina, United States
Ziekenhuis Netwerk Antwerpen Campus Stuivenberg
🇧🇪Antwerpen, Belgium
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Medical University of South Carolina/Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Universitatsklinikum Koln
🇩🇪Köln, Germany
Azienda Ospedaliero-Univesitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Edith Wolfson Medical Center
🇮🇱Holon, Israel
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikat Kozpont
🇭🇺Szeged, Hungary
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Seoul National University Hospital
🇰🇷Jongno-gu, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
North West London Hospitals NHS Trust
🇬🇧Middlesex, United Kingdom
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Hospital Universitaro de Salamanca
🇪🇸Salamanca, Spain
National Cheng-Kung University Hospital
🇨🇳Tainan, Taiwan
Marien Hospital Dusseldorf GmbH
🇩🇪Dusseldorf, Germany
Chonbuk National University Hospital
🇰🇷Jeonju-si, Korea, Republic of
Azienda Ospedaliera Ospedali Riuniti Marche Nord
🇮🇹Pesaro, Italy
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
SPZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱Warszawa, Poland
Memorial Cancer Institute
🇺🇸Miami, Florida, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Texas Oncology - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Università degli Studi di Roma "La Sapienza, Policlinico Umberto I
🇮🇹Roma, Italy
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Centre Hospitalier Luxembourg - CHL Centre
🇱🇺Luxembourg, Luxembourg
County Durham and Darlington NHS Foundation Trust
🇬🇧Darlington, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika
🇭🇺Debrecen, Hungary
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
Shands Cancer Center / University of Florida
🇺🇸Gainesville, Florida, United States
Florida Center for Cellular Therapy / Blood and Marrow Transplant Center
🇺🇸Orlando, Florida, United States
OnCare Hawaii
🇺🇸Honolulu, Hawaii, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
James P. Wilmot Cancer Center / University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
St George Hospital
🇦🇺Kogarah, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Monash Medical Centre
🇦🇺Clayton, Australia
Sunshine Hospital
🇦🇺St Albans, Australia
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Az Sint-Jane Brugge - Oostende Av - Campus Sint-Jan
🇧🇪Brugge, Belgium
Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
🇨🇿Hradec Kralove, Czechia
Cliniques Universitaires UCL de Mont-Goddine
🇧🇪Yvoir, Belgium
AZ Delta - Campus Wilgenstraat
🇧🇪Roeselare, Belgium
Ustav hematologie a krevni transfuze
🇨🇿Praha 2, Czechia
Fakultni Nemocnice Ostrava
🇨🇿Ostrava - Poruba, Czechia
Centre Hospitalier Victor Dupouy d'Argenteuil
🇫🇷Argenteuil Cedex, France
Center Hospitalier Universitaire d' Angers
🇫🇷Angers Cedex 9, France
CHU Amiens Picardie - Site Sud
🇫🇷Amiens Cedex 1, France
Centre Hospitalier Universitaire Hopital Avicenne
🇫🇷Bobigny Cedex, France
Hopital d'Instruction des Armees - Percy
🇫🇷Clamart Cedex, France
Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren
🇫🇷Limoges Cedex, France
Hopital Emile Muller
🇫🇷Mulhouse Cedex, France
Centre Hospitalier Universitaire Nantes-Hotel Dieu
🇫🇷Nantes cedex 1, France
Hopital Saint-Louis / Service d'Hematologie
🇫🇷Paris Cedex 10, France
CHU de Nice - Hopital l'Archet
🇫🇷Nice, France
CHU Bordeaux Hopital Haut-Levaque
🇫🇷Pessac Cedex, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite Cedex, France
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers Cedex, France
Universitatsklinik Freiburg
🇩🇪Freiburg, Germany
Centre Hospitalier Universitaire de Rennes, Hopital Pontchaillou
🇫🇷Rennes Cedex 9, France
Stadtisches Klinikum Braunschweig gGmbH
🇩🇪Braunschweig, Germany
Bacs-Kiskun Megyei Korhaz Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Oktato Korhaza
🇭🇺Kecskemet, Hungary
Carmel Medical Center
🇮🇱Haifa, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Soroka Medical Center, Dept. of Oncology
🇮🇱Beer Sheva, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Seoul Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital de la Santa Creu i Sant Paul
🇪🇸Barcelona, Spain
Hospital Universitario de Girona Doctor Josep Trueta
🇪🇸Girona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
University Hospitals of North Midlands NHS Trust
🇬🇧Stoke on Trent, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States