Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— CASCADE  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02785900
• Other study ID #: SGN33A-005
• Secondary ID: 2015-003482-28
• Status: Terminated
• Phase: Phase 3
• Start date: May 2016
• Est. completion date: October 3, 2017

Study information

• Verified date: November 2018
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 240
• Est. completion date: October 3, 2017
• Est. primary completion date: October 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• 33A
33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push
• placebo
Volume equivalent to 10 mcg/kg, every 4 weeks via IV push
• azacitidine
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks
• decitabine
20 mg/m2 given IV x 5 days, every 4 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Luxembourg,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Time from randomization to death due to any cause	Up to 1.5 years
Primary	Composite Complete Remission (CRc) Rate	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.	Up to 1.5 years
Secondary	Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate	Number of patients who achieve both remission (CR or CRi) and MRD-negative status	Up to 1.5 years
Secondary	Duration of Remission	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.	Up to approximately 9.5 months
Secondary	Event-free Survival	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.	Up to approximately 11.24 months
Secondary	Leukemia-free Survival	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.	Up to approximately 9.49 months
Secondary	Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events	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.	Up to 1.5 years
Secondary	Incidence of Grade 3 or Higher Laboratory Abnormalities	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)	Up to 1.5 years
Secondary	Time to Complete Remission	Time to CR or CRi is the time from randomization to the first documentation of CR/CRi	Up to 1.5 years
Secondary	Mortality Rates at Day 30 and Day 60	30- and 60-day survival from date of randomization. Estimated using Kaplan-Meier method.	Up to 60 days