Clinical trial NCT02785900: Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Official title: A Randomized, Double-blind Phase 3 Study of Vadastuximab Talirine (SGN-CD33A) Versus Placebo in Combination With Azacitidine or Decitabine in the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: Antibodies, monoclonal
Antibody drug conjugate
Antigens, cluster of differentiation 33 (CD33)
Drug therapy
Immunotherapy
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2016-05-30
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 1.5 years
measure: Composite Complete Remission (CRc) Rate
timeFrame: Up to 1.5 years
Secondary outcomes:
measure: Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate
timeFrame: Up to 1.5 years
measure: Duration of Remission
timeFrame: Up to approximately 9.5 months
measure: Event-free Survival
timeFrame: Up to approximately 11.24 months
measure: Leukemia-free Survival
timeFrame: Up to approximately 9.49 months
measure: Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events
timeFrame: Up to 1.5 years
measure: Incidence of Grade 3 or Higher Laboratory Abnormalities
timeFrame: Up to 1.5 years
measure: Time to Complete Remission
timeFrame: Up to 1.5 years
measure: Mortality Rates at Day 30 and Day 60
timeFrame: Up to 60 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South Region
state: Florida
city: Gainesville
country: United States
facility: Shands Cancer Center / University of Florida
state: Florida
city: Miami
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Florida Center for Cellular Therapy / Blood and Marrow Transplant Center
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Honolulu
country: United States
facility: OnCare Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health Sciences Center / Feist Weiller Cancer Center
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center / University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina/Hollings Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital / Bon Secours
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Blood and Marrow Transplant/Acute Leukemia Program
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Kogarah
country: Australia
facility: St George Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: St Albans
country: Australia
facility: Sunshine Hospital
city: Salzburg
country: Austria
facility: LKH Salzburg, Universitatsklinikum der PMU
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Campus Stuivenberg
city: Brugge
country: Belgium
facility: Az Sint-Jane Brugge - Oostende Av - Campus Sint-Jan
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire Sart Tilman Liege
city: Roeselare
country: Belgium
facility: AZ Delta - Campus Wilgenstraat
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Goddine
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
city: Ostrava - Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Ustav hematologie a krevni transfuze
city: Amiens Cedex 1
country: France
facility: CHU Amiens Picardie - Site Sud
city: Angers Cedex 9
country: France
facility: Center Hospitalier Universitaire d' Angers
city: Argenteuil Cedex
country: France
facility: Centre Hospitalier Victor Dupouy d'Argenteuil
city: Bobigny Cedex
country: France
facility: Centre Hospitalier Universitaire Hopital Avicenne
city: Clamart Cedex
country: France
facility: Hopital d'Instruction des Armees - Percy
city: Lille cedex
country: France
facility: CHRU de Lille
city: Limoges Cedex
country: France
facility: Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren
city: Mulhouse Cedex
country: France
facility: Hopital Emile Muller
city: Nantes cedex 1
country: France
facility: Centre Hospitalier Universitaire Nantes-Hotel Dieu
city: Nice
country: France
facility: CHU de Nice - Hopital l'Archet
city: Paris Cedex 10
country: France
facility: Hopital Saint-Louis / Service d'Hematologie
city: Pessac Cedex
country: France
facility: CHU Bordeaux Hopital Haut-Levaque
city: Pierre Bénite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers Cedex
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rennes Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Rennes, Hopital Pontchaillou
city: Braunschweig
country: Germany
facility: Stadtisches Klinikum Braunschweig gGmbH
city: Dusseldorf
country: Germany
facility: Marien Hospital Dusseldorf GmbH
city: Freiburg
country: Germany
facility: Universitatsklinik Freiburg
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Universitatsklinikum Koln
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos Ã©s Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Oktato Korhaza
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikat Kozpont
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Sheva
country: Israel
facility: Soroka Medical Center, Dept. of Oncology
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Univesitaria San Luigi Gonzaga
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
city: Roma
country: Italy
facility: Università degli Studi di Roma "La Sapienza, Policlinico Umberto I
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Jeonju-si
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier Luxembourg - CHL Centre
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Paul
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Girona
country: Spain
facility: Hospital Universitario de Girona Doctor Josep Trueta
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital Universitaro de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Darlington
country: United Kingdom
facility: County Durham and Darlington NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Middlesex
country: United Kingdom
facility: North West London Hospitals NHS Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Stoke on Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS Trust
Study officials:
affiliation: Seagen Inc.
name: Phoenix Ho, MD
role: STUDY_DIRECTOR
References: