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A Safety Study of SGN-CD33A in Combination With Standard-of-care in Patients With AML

Phase 1
Completed
Conditions
Acute Myeloid Leukemia
Acute Myelogenous Leukemia
Interventions
Registration Number
NCT02326584
Lead Sponsor
Seagen Inc.
Brief Summary

This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) by itself (monotherapy) or in combination with other standard treatments. The main purpose of this study is to find the best dose and schedule for SGN-CD33A when given in combination with standard induction treatment, in combination with standard consolidation treatment, or by itself for maintenance treatment. This will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.

Detailed Description

The study will be conducted in the following distinct parts:

Part A: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 and Day 4 dosing)

Part B: Consolidation dose escalation - consolidation combined with SGN-CD33A; up to 4 cycles of consolidation therapy will be administered after SGN-CD33A (Day 1 of each cycle).

Part C: Maintenance - SGN-CD33A Monotherapy; Up to 24 patients with and up to 24 patient without prior allogeneic stem cell transplant will be treated with SGN-CD33A. Both arms will enroll simultaneously. SGN-CD33A will be administered on Day 1 of each 6-week cycle for up to 8 cycles.

Part D: Induction plus consolidation - induction/consolidation combined with SGN-CD33A; patients who achieve a CR/CRi (with or without a second induction) will receive up to 4 cycles of consolidation therapy administered after SGN-CD33A (Day 1 of each cycle).

Part E: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 dosing)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
116
Inclusion Criteria
  • All subtypes of Acute Myeloid leukemia (except for acute promyelocytic leukemia)
  • Eastern Cooperative Oncology Group status of 0 or 1
  • Adequate baseline renal and hepatic function
  • Central venous access
  • Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance
Exclusion Criteria
  • Previous treatment for MDS or MPN for dose escalation cohorts
  • Inadequate lung function
  • Inadequate heart function

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Consolidation with SGN-CD33AHigh dose cytarabine for consolidationHigh dose cytarabine for consolidation + SGN-CD33A (28-day cycles)
Induction with SGN-CD33ASGN-CD33A7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
Induction and Consolidation with SGN-CD33AStandard dose cytarabine for induction7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
Induction and Consolidation with SGN-CD33ADaunorubicin7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
Induction with SGN-CD33AStandard dose cytarabine for induction7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
Induction with SGN-CD33ADaunorubicin7+3 (Standard dose cytarabine for induction and daunorubicin) + SGN-CD33A
Consolidation with SGN-CD33ASGN-CD33AHigh dose cytarabine for consolidation + SGN-CD33A (28-day cycles)
Induction and Consolidation with SGN-CD33AHigh dose cytarabine for consolidation7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
SGN-CD33A MaintenanceSGN-CD33ASGN-CD33A Monotherapy (42-day cycles)
Induction and Consolidation with SGN-CD33ASGN-CD33A7+3 (standard dose cytarabine for induction and daunorubicin) + SGN-CD33A and High dose cytarabine for consolidation + SGN-CD33A
Primary Outcome Measures
NameTimeMethod
Incidence of adverse eventsThrough 1 month following last dose
Incidence of laboratory abnormalitiesThrough 1 month following last dose
Incidence of dose-limiting toxicity (DLT)Through 1 month following last dose
Secondary Outcome Measures
NameTimeMethod
Complete remission (CR) rate at the end of inductionThrough 1 month following last dose
Blood concentrations of SGN-CD33A and metabolitesUp to approximately 3 years
Incidence of antitherapeutic antibodies (ATA)Up to approximately 3 years
Leukemia-free survivalUp to approximately 3 years
Overall survivalUp to approximately 3 years
Rate of minimal residual disease (MRD) clearanceUp to approximately 3 years

Trial Locations

Locations (13)

James Cancer Hospital / Ohio State University

🇺🇸

Columbus, Ohio, United States

Cardinal Bernardin Cancer Center / Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

Charles A. Sammons Cancer Center / Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Cleveland Clinic, The

🇺🇸

Cleveland, Ohio, United States

MD Anderson Cancer Center / University of Texas

🇺🇸

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

🇺🇸

Seattle, Washington, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Karmanos Cancer Institute / Wayne State University

🇺🇸

Detroit, Michigan, United States

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

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