Clinical trial NCT02326584: A Safety Study of SGN-CD33A in Combination With Standard-of-care in Patients With AML
Official title: A Phase 1b Dose-escalation Study of SGN-CD33A in Combination With Standard-of-care for Patients With Newly Diagnosed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Myelogenous Leukemia
Keywords: Acute Myeloid Leukemia
Antibody-Drug Conjugate
CD33 Antigen
Drug Therapy
Acute Myelogenous Leukemia
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2014-12-29
Enrollment: 116
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) 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)

Eligibility criteria: 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

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
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: Through 1 month following last dose
Secondary outcomes:
measure: Complete remission (CR) rate at the end of induction
timeFrame: Through 1 month following last dose
measure: Leukemia-free survival
timeFrame: Up to approximately 3 years
measure: Overall survival
timeFrame: Up to approximately 3 years
measure: Blood concentrations of SGN-CD33A and metabolites
timeFrame: Up to approximately 3 years
measure: Incidence of antitherapeutic antibodies (ATA)
timeFrame: Up to approximately 3 years
measure: Rate of minimal residual disease (MRD) clearance
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: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center / Loyola University Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic, The
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
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: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Seagen Inc.
name: Eric Feldman, MD
role: STUDY_DIRECTOR
References: