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: Drug: vadastuximab talirine; Drug: Placebo (for 33A); Drug: Azacitidine

• 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.

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-19
• Study First Submitted QC: 2016-03-08
• Study First Posted: 2016-03-11
• Primary Completion: 2017-11-06
• Study Completion: 2017-11-06
• Results First Submitted: 2018-10-18
• Results First Submitted QC: 2018-12-20
• Results First Posted: 2018-12-21
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-23
• Last Update Posted: 2019-02-12

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

Group	Intervention	Description
Placebo + azacitidine	Placebo (for 33A)	placebo plus azacitidine
33A + azacitidine	vadastuximab talirine	Vadastuximab talirine plus azacitidine
33A + azacitidine	Azacitidine	Vadastuximab talirine plus azacitidine
Placebo + azacitidine	Azacitidine	placebo plus azacitidine

Primary Outcome Measures

Name	Time	Method
Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study	Up 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 Study	N/A - End point not assessed

Secondary Outcome Measures

Name	Time	Method
Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities	Up 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) Rate	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 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) Rate	N/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)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Cancer Centers, LLP; 🇺🇸 Aurora, Colorado, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

University of Colorado Hospital; 🇺🇸 Denver, Colorado, United States

Cancer Specialisits of North Florida; 🇺🇸 Fleming Island, Florida, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Georgia Regents University Hospital; 🇺🇸 Augusta, Georgia, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

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