Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS

A Phase 1/2 Study of Vadastuximab Talirine (SGN-CD33A) in Combination With Azacitidine in Patients With Previously Untreated International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk Myelodysplastic Syndrome (MDS)

This is a phase 1/2 study to evaluate the combination of vadastuximab talirine (SGN-CD33A; 33A) and azacitidine in subjects with previously untreated International Prognostic Scoring System (IPSS) Intermediate-2 or high risk myelodysplastic syndrome (MDS).

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: vadastuximab talirine; Drug: Azacitidine; Drug: Placebo (for 33A)

Detailed Description

In the phase 1 portion of the study, escalating doses of 33A will be evaluated in combination with azacitidine, and a dose of 33A will be selected to proceed to phase 2. The phase 2 portion of the study is randomized, double-blind and placebo-controlled; it is designed to compare the overall response rate (ORR) between 2 study arms.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Aurora, Colorado, United States
      • Rocky Mountain Cancer Centers, LLP
    • Denver, Colorado, United States
      • University of Colorado Hospital
    • Denver, Colorado, United States
      • Colorado Blood Cancer Institute
  • Florida
    • Fleming Island, Florida, United States
      • Cancer Specialisits of North Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Augusta, Georgia, United States
      • Georgia Regents University Hospital
  • Illinois
    • Chicago, Illinois, United States
      • Rush University Medical Center
  • Maryland
    • Bethesda, Maryland, United States
      • Center for Cancer and Blood Disorders
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States
      • Barbara Ann Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States
      • University of Minnesota Medical Center (UMMC)
  • Montana
    • Bozeman, Montana, United States
      • Bozeman Deaconess Health Group
  • New Jersey
    • Hackensack, New Jersey, United States
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States
      • The University of New Mexico Cancer Research and Treatment Center
  • New York
    • Brooklyn, New York, United States
      • Weill Cornell
    • Hawthorne, New York, United States, 10532
      • Westchester Medical Center
    • New York, New York, United States
      • Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina At Chapel Hill
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cleveland, Ohio, United States
      • Case Western Reserve University (CWRU) - University Hospitals Case Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science
    • Portland, Oregon, United States, 97213
      • Providence Portland Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • University of Pennsylvania, Abramson Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States
      • Tennessee Oncology, PLLC
  • Texas
    • Austin, Texas, United States
      • Texas Oncology - Austin Midtown
    • Dallas, Texas, United States
      • Baylor University Medical Center
    • Houston, Texas, United States
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States
      • Cancer Care Centers of South Texas
  • Washington
    • Seattle, Washington, United States
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Froedtert & Medical College of Wisconson Clinical Cancer Center

Participation Criteria

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:

• Subjects with cytologically/histologically confirmed MDS according to the World Health Organization (WHO) 2008 classification.
• Previously untreated for Myelodysplastic Syndrome (MDS)
• Age ≥18 years of age.
• Eligible for therapy with azacitidine.
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Adequate baseline laboratory parameters.

Exclusion Criteria:

• Received prior treatment for MDS with lenalidomide or hypomethylating agents (HMAs).
• History of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis.
• Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, eg, prostate or breast cancer).
• Candidates for allogeneic stem cell transplant at the time of screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 33A + azacitidine; Vadastuximab talirine plus azacitidine	Drug: vadastuximab talirine; Intravenous (IV) push every 4 weeks; Other Names: 33A; SGN-CD33A; Drug: Azacitidine; 75 mg/m^2 given intravenously or subcutaneously for 7 days every 4 weeks
Active Comparator: Placebo + azacitidine; placebo plus azacitidine	Drug: Azacitidine; 75 mg/m^2 given intravenously or subcutaneously for 7 days every 4 weeks; Drug: Placebo (for 33A); Placebo supplied in single-use vials matching 33A, IV push every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study	A recommended dose of vadastuximab talirine was not identified in Phase 1 due to study termination. Number of dose delays and reductions are reported in lieu of a dose recommendation.	Up to 1 year
Phase 2 Outcome Measure: Overall Response Rate for the Phase 2 Portion of the Study		N/A - End point not assessed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities	As defined by the number of participants with adverse events and laboratory abnormalities. Participants are included only once per row, even if the participant experienced multiple events applicable to the category.	Up to 1 year
Complete Response Rate (CR)	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the CR rate, as defined by the 2006 IWG criteria for MDS.	N/A - End point not assessed
Hematologic Improvement (HI) Rate	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the HI rate, as defined by the 2006 IWG criteria for MDS.	N/A - End point not assessed
Duration of Response (DOR) Rate	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first observation of response (CR, PR, or Marrow CR) to disease progression/relapse or death from any cause, whichever occurs first.	N/A - End point not assessed
Progression Free Survival (PFS)	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first.	N/A - End point not assessed
Rate of Transformation to Acute Myeloid Leukemia (AML)	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the rate of transformation to AML after initiation of study therapy.	N/A - End point not assessed
Overall Survival (OS)	Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to death due to any cause.	N/A - End point not assessed

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Chair: Phillip Garfin, Seagen Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): November 6, 2017
• Study Completion (Actual): November 6, 2017

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: March 8, 2016
• First Posted (Estimate): March 11, 2016

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: January 23, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Antibody-Drug Conjugate CD33 Antigen
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: SGN33A-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes