A Safety Study of SGN-CD33A in AML Patients
- Conditions
- Acute Myelogenous LeukemiaAcute Myeloid LeukemiaAcute Promyelocytic Leukemia
- Interventions
- Drug: HMA
- Registration Number
- NCT01902329
- Lead Sponsor
- Seagen Inc.
- Brief Summary
This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) administered as a single agent and in combination with a hypomethylating agent (HMA). The main purpose of the study is to find the maximum tolerated dose (MTD, which is the highest dose that does not cause unacceptable side effects) of SGN-CD33A in patients with acute myeloid leukemia (AML). The MTD 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-leukemia activity of SGN-CD33A will be assessed.
- Detailed Description
This study will explore SGN-CD33A as a monotherapy and in combination with a hypomethylating agent (HMA; i.e., azacitidine or decitabine). Initial study treatment with SGN-CD33A includes a maximum of 2 cycles of treatment for monotherapy and 4 cycles for combination cohorts. Patients who achieve documented CR or CRi (Monotherapy) or clinical benefit (Combination) during the first part of the study are eligible to continue treatment.
Additional monotherapy cohorts may include patients with relapsed acute promyelocytic leukemia, relapsed patients with nucleophosmin-1 gene mutation (absence of fms-like tyrosine kinase 3 mutation) (NPM1-mutated, FLT-3 wild type), alternate dosing schedules (fractionated dosing on Days 1 and 4), treatment naive patients with AML who declined intensive therapy, and patients who have relapsed after post-allogeneic stem cell transplant.
Patients in the combination cohort will be treated with azacitidine or decitabine per institutional practice prior to SGN-CD33A dosing. Expansion cohorts may be added for further evaluation of safety, pharmacokinetics, pharmacodynamics, and antitumor activity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- Acute myeloid leukemia, positive for CD33
- Eastern Cooperative Oncology Group status of 0 or 1
- Adequate baseline renal and hepatic function
- Central venous access
- Either achieved complete remission (greater than 12 weeks in duration) with initial induction/consolidation and have experienced relapse of disease or declined treatment with high-dose induction/consolidation
- Bone marrow blasts greater than or equal to 5% for relapsed patients, or greater than or equal to 20% for untreated patients
- Inadequate lung function
- Prior allogeneic stem cell transplant, except for a specific cohort
- High-dose chemotherapy within 4 weeks of study drug
- Antileukemia treatment within 14 days of study drug (other than hydroxyurea or 6-mercaptopurine)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SGN-CD33A + HMA HMA SGN-CD33A with hypomethylating agent SGN-CD33A + HMA SGN-CD33A SGN-CD33A with hypomethylating agent SGN-CD33A Monotherapy SGN-CD33A SGN-CD33A
- Primary Outcome Measures
Name Time Method Incidence of adverse events Through 1 month following last dose Incidence of laboratory abnormalities Through 1 month following last dose
- Secondary Outcome Measures
Name Time Method Rate of complete remission Up to 3 months Incidence of antitherapeutic antibodies Through 1 month following last dose Relapse-free survival Up to approximately 3 years Overall survival Up to approximately 3 years Blood concentrations of SGN-CD33A and metabolites Through 3 weeks after dosing Duration of complete remission Up to approximately 3 years
Trial Locations
- Locations (14)
Winship Cancer Institute / Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Cleveland Clinic, The
🇺🇸Cleveland, Ohio, United States
Charles A. Sammons Cancer Center / Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States