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

Phase 1
Terminated
Conditions
Myelodysplastic Syndrome
Interventions
Registration Number
NCT02706899
Lead Sponsor
Seagen Inc.
Brief Summary

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).

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
19
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + azacitidinePlacebo (for 33A)placebo plus azacitidine
33A + azacitidinevadastuximab talirineVadastuximab talirine plus azacitidine
33A + azacitidineAzacitidineVadastuximab talirine plus azacitidine
Placebo + azacitidineAzacitidineplacebo plus azacitidine
Primary Outcome Measures
NameTimeMethod
Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the StudyUp to 1 year

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.

Phase 2 Outcome Measure: Overall Response Rate for the Phase 2 Portion of the StudyN/A - End point not assessed
Secondary Outcome Measures
NameTimeMethod
Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory AbnormalitiesUp to 1 year

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.

Complete Response Rate (CR)N/A - End point not assessed

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.

Duration of Response (DOR) RateN/A - End point not assessed

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.

Overall Survival (OS)N/A - End point not assessed

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.

Hematologic Improvement (HI) RateN/A - End point not assessed

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.

Progression Free Survival (PFS)N/A - End point not assessed

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.

Rate of Transformation to Acute Myeloid Leukemia (AML)N/A - End point not assessed

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.

Trial Locations

Locations (34)

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Ohio State University

🇺🇸

Columbus, Ohio, United States

Case Western Reserve University (CWRU) - University Hospitals Case Medical Center

🇺🇸

Cleveland, Ohio, United States

Banner MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Georgia Regents University Hospital

🇺🇸

Augusta, Georgia, United States

Cancer Specialisits of North Florida

🇺🇸

Fleming Island, Florida, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

Center for Cancer and Blood Disorders

🇺🇸

Bethesda, Maryland, United States

Texas Oncology - Austin Midtown

🇺🇸

Austin, Texas, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

The University of New Mexico Cancer Research and Treatment Center

🇺🇸

Albuquerque, New Mexico, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Wake Forest Baptist Health

🇺🇸

Winston-Salem, North Carolina, United States

Providence Portland Research Center

🇺🇸

Portland, Oregon, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Tennessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

University of Colorado Hospital

🇺🇸

Denver, Colorado, United States

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Cancer Care Centers of South Texas

🇺🇸

San Antonio, Texas, United States

Rocky Mountain Cancer Centers, LLP

🇺🇸

Aurora, Colorado, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

University of Minnesota Medical Center (UMMC)

🇺🇸

Minneapolis, Minnesota, United States

Bozeman Deaconess Health Group

🇺🇸

Bozeman, Montana, United States

Weill Cornell

🇺🇸

Brooklyn, New York, United States

Westchester Medical Center

🇺🇸

Hawthorne, New York, United States

University of Pennsylvania, Abramson Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Oregon Health & Science

🇺🇸

Portland, Oregon, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

Froedtert & Medical College of Wisconson Clinical Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

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