A Safety Study of SGN-CD33A in AML Patients

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Seattle Genetics, Inc.
ClinicalTrials.gov Identifier:
NCT01902329
First received: July 15, 2013
Last updated: March 23, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Acute Myelogenous Leukemia
Acute Myeloid Leukemia
Acute Promyelocytic Leukemia
Drug: HMA
Drug: SGN-CD33A
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of SGN-CD33A in Patients With CD33-positive Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Seattle Genetics, Inc.:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Through 1 month following last dose ] [ Designated as safety issue: Yes ]
  • Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Blood concentrations of SGN-CD33A and metabolites [ Time Frame: Through 3 weeks after dosing ] [ Designated as safety issue: No ]
  • Incidence of antitherapeutic antibodies [ Time Frame: Through 1 month following last dose ] [ Designated as safety issue: Yes ]
  • Rate of complete remission [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Duration of complete remission [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Relapse-free survival [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to approximately 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 225
Study Start Date: July 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SGN-CD33A + HMA
SGN-CD33A with hypomethylating agent
Drug: HMA
azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days
Drug: SGN-CD33A
Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)
Other Name: vadastuximab talirine
Experimental: SGN-CD33A Monotherapy
SGN-CD33A
Drug: SGN-CD33A
Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)
Other Name: vadastuximab talirine

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01902329

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Cleveland Clinic, The
Cleveland, Ohio, United States, 44195
United States, Texas
Charles A. Sammons Cancer Center / Baylor University Medical Center
Dallas, Texas, United States, 75246
MD Anderson Cancer Center / University of Texas
Houston, Texas, United States, 77030-4095
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Seattle Genetics, Inc.
Investigators
Study Director: Phoenix Ho, MD Seattle Genetics, Inc.
  More Information

Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT01902329     History of Changes
Other Study ID Numbers: SGN33A-001 
Study First Received: July 15, 2013
Last Updated: March 23, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Seattle Genetics, Inc.:
Acute Myeloid Leukemia
Antibody-Drug Conjugate
CD33 Antigen
Immunotherapy
Drug Therapy
Acute Myelogenous Leukemia
Acute Promyelocytic Leukemia
APL

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Promyelocytic, Acute
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on May 03, 2016