Clinical trial NCT01902329: A Safety Study of SGN-CD33A in AML Patients
Official title: A Phase 1 Trial of SGN-CD33A in Patients With CD33-positive Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Acute Myeloid Leukemia
Acute Promyelocytic Leukemia
Keywords: Acute Myeloid Leukemia
Antibody-Drug Conjugate
CD33 Antigen
Immunotherapy
Drug Therapy
Acute Myelogenous Leukemia
Acute Promyelocytic Leukemia
APL
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-18
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Through 1 month following last dose
measure: Incidence of laboratory abnormalities
timeFrame: Through 1 month following last dose
Secondary outcomes:
measure: Blood concentrations of SGN-CD33A and metabolites
timeFrame: Through 3 weeks after dosing
measure: Incidence of antitherapeutic antibodies
timeFrame: Through 1 month following last dose
measure: Rate of complete remission
timeFrame: Up to 3 months
measure: Duration of complete remission
timeFrame: Up to approximately 3 years
measure: Relapse-free survival
timeFrame: Up to approximately 3 years
measure: Overall survival
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic, The
state: Ohio
city: Dallas
country: United States
facility: Charles A. Sammons Cancer Center / Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Seagen Inc.
name: Phoenix Ho, MD
role: STUDY_DIRECTOR
References:
citation: Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, Ravandi F, Kovacsovics T, DeAngelo DJ, Bixby D, Faderl S, Jillella AP, Ho PA, O'Meara MM, Zhao B, Biddle-Snead C, Stein AS. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018 Jan 25;131(4):387-396. doi: 10.1182/blood-2017-06-789800. Epub 2017 Dec 1.