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

November 21, 2018 updated by: Seagen Inc.

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Royal Adelaide Hospital
      • Clayton, Australia, 3168
        • Monash Medical Centre
      • Kogarah, Australia, 2217
        • St George Hospital
      • Perth, Australia, 6000
        • Royal Perth Hospital
      • St Albans, Australia, 3021
        • Sunshine Hospital
  • Austria
      • Salzburg, Austria, 5020
        • LKH Salzburg, Universitatsklinikum der PMU
      • Wels, Austria, 4600
        • Klinikum Wels-Grieskirchen GmbH
  • Belgium
      • Antwerpen, Belgium, 2060
        • Ziekenhuis Netwerk Antwerpen Campus Stuivenberg
      • Brugge, Belgium, 8000
        • Az Sint-Jane Brugge - Oostende Av - Campus Sint-Jan
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint Luc
      • Bruxelles, Belgium, 1000
        • Institut Jules Bordet
      • Liege, Belgium, 4000
        • Centre Hospitalier Universitaire Sart Tilman Liège
      • Roeselare, Belgium, 8800
        • AZ Delta - Campus Wilgenstraat
      • Yvoir, Belgium, 5530
        • Cliniques Universitaires UCL de Mont-Goddine
  • Czechia
      • Brno, Czechia, 625 00
        • Fakultni nemocnice Brno
      • Hradec Kralove, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
      • Ostrava - Poruba, Czechia, 708 52
        • Fakultni nemocnice Ostrava
      • Praha 2, Czechia, 128 20
        • Ustav hematologie a krevni transfuze
  • France
      • Amiens Cedex 1, France, 80054
        • CHU Amiens Picardie - Site Sud
      • Angers Cedex 9, France, 49933
        • Center Hospitalier Universitaire d' Angers
      • Argenteuil Cedex, France, 95107
        • Centre Hospitalier Victor Dupouy d'Argenteuil
      • Bobigny Cedex, France, 93009
        • Centre Hospitalier Universitaire Hopital Avicenne
      • Clamart Cedex, France, 92141
        • Hôpital d'instruction des armées - Percy
      • Lille cedex, France, 59037
        • CHRU de Lille
      • Limoges Cedex, France, 87042
        • Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren
      • Mulhouse Cedex, France, 68070
        • Hôpital Emile Muller
      • Nantes cedex 1, France, 44093
        • Centre Hospitalier Universitaire Nantes-Hotel Dieu
      • Nice, France, 06200
        • CHU de Nice - Hopital L'Archet
      • Paris Cedex 10, France, 75475
        • Hopital Saint-Louis / Service d'Hematologie
      • Pessac Cedex, France, 33604
        • CHU Bordeaux Hopital Haut-Levaque
      • Pierre Bénite Cedex, France, 69495
        • Centre Hospitalier Lyon Sud
      • Poitiers Cedex, France, 86021
        • Centre Hospitalier Universitaire de Poitiers
      • Rennes Cedex 9, France, 35033
        • Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
  • Germany
      • Braunschweig, Germany, 38114
        • Städtisches Klinikum Braunschweig gGmbH
      • Dusseldorf, Germany, 40479
        • Marien Hospital Dusseldorf GMBH
      • Freiburg, Germany, 79106
        • Universitätsklinik Freiburg
      • Kiel, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein
      • Köln, Germany, 50937
        • Universitätsklinikum Köln
  • Hungary
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem
      • Debrecen, Hungary, 4004
        • Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum, III. sz. Belgyogyaszati Klinika
      • Kaposvár, Hungary, 7400
        • Somogy Megyei Kaposi Mór Oktató Kórház
      • Kecskemet, Hungary, 6000
        • Bacs-Kiskun Megyei Korhaz Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Oktato Korhaza
      • Szeged, Hungary, 6720
        • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikat Kozpont
  • Israel
      • Ashkelon, Israel, 78278
        • Barzilai Medical Center
      • Beer Sheva, Israel, 84101
        • Soroka Medical Center, Dept. of Oncology
      • Haifa, Israel, 34362
        • Carmel Medical Center
      • Holon, Israel, 58100
        • Edith Wolfson Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center
      • Jerusalem, Israel, 91031
        • Shaare Zedek Medical Center
      • Petach Tikva, Israel, 49414
        • Rabin Medical Center
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Milano, Italy, 20122
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
      • Orbassano, Italy, 10043
        • Azienda Ospedaliero-Univesitaria San Luigi Gonzaga
      • Pesaro, Italy, 61100
        • Azienda Ospedaliera Ospedali Riuniti Marche Nord
      • Roma, Italy, 00161
        • Università degli Studi di Roma "La Sapienza, Policlinico Umberto I
  • Korea, Republic of
      • Daegu, Korea, Republic of, 700-712
        • Keimyung University Dongsan Medical Center
      • Daegu, Korea, Republic of, 705-703
        • Yeungnam University Medical Center
      • Daejeon, Korea, Republic of, 301-721
        • Chungnam National University Hospital
      • Hwasun, Korea, Republic of, 519-763
        • Chonnam National University Hwasun Hospital
      • Jeonju-si, Korea, Republic of, 561-712
        • Chonbuk National University Hospital
      • Jongno-gu, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 152-703
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of, 120-752
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 137-701
        • Seoul Saint Mary's Hospital
  • Luxembourg
      • Luxembourg, Luxembourg, 1210
        • Centre Hospitalier Luxembourg - CHL Centre
  • Poland
      • Krakow, Poland, 31-501
        • SPZOZ Szpital Uniwersytecki w Krakowie
      • Warszawa, Poland, 02-097
        • Samodzielny Publiczny Centralny Szpital Kliniczny
  • Spain
      • Badalona, Spain, 08916
        • Hospital Universitari Germans Trias I Pujol
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Paul
      • Caceres, Spain, 10002
        • Hospital San Pedro de Alcantara
      • Girona, Spain, 17007
        • Hospital Universitario de Girona Doctor Josep Trueta
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Malaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Salamanca, Spain, 37007
        • Hospital Universitaro de Salamanca
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe de Valencia
  • Taiwan
      • Changhua, Taiwan, 50006
        • Changhua Christian Hospital
      • Tainan, Taiwan, 70403
        • National Cheng-Kung University Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • United Kingdom
      • Darlington, United Kingdom, DL3 6HX
        • County Durham and Darlington NHS Foundation Trust
      • London, United Kingdom, W12 0HS
        • Imperial College Healthcare NHS Trust
      • Middlesex, United Kingdom, HA1 3UJ
        • North West London Hospitals NHS Trust
      • Newcastle Upon Tyne, United Kingdom, NE7 7DN
        • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Southampton, United Kingdom, SO16 6YD
        • University Hospital Southampton NHS Foundation Trust
      • Stoke on Trent, United Kingdom, ST4 6QG
        • University Hospitals of North Midlands NHS Trust
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope National Medical Center
      • San Francisco, California, United States, 94115
        • Pacific Hematology Oncology Associates
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists - South Region
      • Gainesville, Florida, United States, 32610
        • Shands Cancer Center / University of Florida
      • Miami, Florida, United States, 33028
        • Memorial Cancer Institute
      • Orlando, Florida, United States, 32804
        • Florida Center for Cellular Therapy / Blood and Marrow Transplant Center
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists - North Region
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • OnCare Hawaii
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637-1470
        • University Of Chicago
    • Kansas
      • Westwood, Kansas, United States, United States
        • University of Kansas Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • LSU Health Sciences Center / Feist Weiller Cancer Center
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer and Blood Disorders
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center / University of Rochester Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina/Hollings Cancer Center
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital / Bon Secours
    • Tennessee
      • Nashville, Tennessee, United States, 30384
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030-4095
        • MD Anderson Cancer Center / University of Texas
      • San Antonio, Texas, United States, 78240
        • Texas Oncology - San Antonio Medical Center
      • San Antonio, Texas, United States, 78234-7679
        • Brooke Army Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • Intermountain Blood and Marrow Transplant/Acute Leukemia Program
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Medical Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 33A + HMA
33A plus azacitidine or decitabine
Drug: 33A
33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push
Other Names:
  • vadastuximab talirine, SGN-CD33A
Drug: azacitidine
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks
Drug: decitabine
20 mg/m2 given IV x 5 days, every 4 weeks
Active Comparator: placebo + HMA
placebo plus azacitidine or decitabine
Drug: azacitidine
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks
Drug: decitabine
20 mg/m2 given IV x 5 days, every 4 weeks
Drug: placebo
Volume equivalent to 10 mcg/kg, every 4 weeks via IV push

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Up to 1.5 years
Time from randomization to death due to any cause
Up to 1.5 years
Composite Complete Remission (CRc) Rate
Time Frame: 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.
Up to 1.5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seagen Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

October 3, 2017

Study Completion (Actual)

October 3, 2017

Study Registration Dates

First Submitted

May 25, 2016

First Submitted That Met QC Criteria

May 25, 2016

First Posted (Estimate)

May 30, 2016

Study Record Updates

Last Update Posted (Actual)

December 12, 2018

Last Update Submitted That Met QC Criteria

November 21, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGN33A-005
  • 2015-003482-28 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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