A Safety Study of SGN-CD33A in AML Patients

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1 Trial of SGN-CD33A in Patients With CD33-positive Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01902329
• Other study ID #: SGN33A-001
• Status: Completed
• Phase: Phase 1
• First received: July 15, 2013
• Last updated: January 3, 2018
• Start date: July 2013
• Est. completion date: December 8, 2017

Study information

• Verified date: January 2018
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: December 8, 2017
• Est. primary completion date: March 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Acute Promyelocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• HMA
azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days
• 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)

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	Charles A. Sammons Cancer Center / Baylor University Medical Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events		Through 1 month following last dose
Primary	Incidence of laboratory abnormalities		Through 1 month following last dose
Secondary	Blood concentrations of SGN-CD33A and metabolites		Through 3 weeks after dosing
Secondary	Incidence of antitherapeutic antibodies		Through 1 month following last dose
Secondary	Rate of complete remission		Up to 3 months
Secondary	Duration of complete remission		Up to approximately 3 years
Secondary	Relapse-free survival		Up to approximately 3 years
Secondary	Overall survival		Up to approximately 3 years