Clinical trial NCT02848248: A Safety Study of SGN-CD123A in Patients With Acute Myeloid Leukemia
Official title: A Phase 1 Study of SGN-CD123A in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Antibody-Drug Conjugate
CD123 Antigen
Drug Therapy
AML
Leukemia, Myeloid, Acute
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will examine the safety profile of SGN-CD123A. The study will test increasing doses of SGN-CD123A given every 3 weeks to patients.

Detailed description: This study is designed to evaluate the safety, tolerability, and preliminary estimate of antitumor activity of SGN-CD123A. The study will be conducted in 2 parts:

1. Part A is the dose-escalation portion of the trial, designed to identify the maximum tolerated dose (MTD) of SGN-CD123A
2. Part B is the dose-expansion portion of the trial, designed to evaluate SGN-CD123A in patients with differing CD123 expression levels

Dose-escalation in Part A will be conducted using a 3+3 study design. Patients with CD123-detectable AML will be enrolled in cohorts at escalating doses of study drug and will receive up to 2 induction cycles of SGN-CD123A treatment at an assigned dose level in 3-week cycles.

After completion of dose-escalation, patients will be enrolled in Part B of the study. Patients enrolled in Part B will receive up to 2 induction cycles of SGN-CD123A treatment at a dose level and frequency determined by results in Part A.

For both Part A and Part B, a third induction cycle may be permitted with the approval of the study medical monitor. If a patient achieves a complete remission or complete remission with incomplete hematologic recovery, optional post-remission cycles of SGN-CD123A may be administered.

Eligibility criteria: Inclusion Criteria:

* Relapsed/refractory acute myeloid leukemia following at least 2 but no more than 3 prior regimens
* Patients may be eligible after only 1 previous regimen if in a high risk category
* Adequate baseline renal and hepatic function
* Eastern Cooperative Oncology Group Status of 0 or 1
* CD123-detectable leukemia

Exclusion Criteria:

* Cerebral/meningeal disease related to underlying malignancy
* Promyelocytic leukemia
* History of clinically significant pulmonary fibrosis or documented diffusing capacity of the lung for carbon monoxide \<50% predicted
* Prior hematopoietic stem cell transplant
* Antileukemia or experimental treatment within 4 weeks of study drug (other than hydroxyurea or 6-mercaptopurine)
* Cardio or cerebral vascular event within 6 months

Primary outcomes:
measure: Type, incidence, severity, seriousness, and relatedness of adverse events
timeFrame: Through 1 month following last dose, or end-of-treatment visit whichever is later
measure: Type, incidence, and severity of laboratory abnormalities
timeFrame: Through 1 month following last dose, or end-of-treatment visit whichever is later
measure: Incidence of dose-limiting toxicity
timeFrame: First cycle of treatment, 3 weeks
Secondary outcomes:
measure: Blood concentrations of SGN-CD123A, total antibodies, and metabolites
timeFrame: Through 1 month following last dose, or end-of-treatment visit whichever is later
measure: Incidence of antitherapeutic antibodies
timeFrame: Through 1 month following last dose, or end-of-treatment visit whichever is later
measure: Rate of remission
timeFrame: Through 1 month following last dose, or end-of-treatment visit whichever is later
measure: Duration of complete remission
timeFrame: Up to approximately 1 year
measure: Leukemia-free survival
timeFrame: Up to approximately 1 year
measure: Overall survival
timeFrame: Up to approximately 1 year
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: Aurora
country: United States
facility: University of Colorado Hospital / University of Colorado
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Hawthorne
country: United States
facility: Hudson Valley Hematology and Oncology Associates/New York Medical College
state: New York
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: Phoenix Ho, MD
role: STUDY_DIRECTOR
References:
citation: Li F, Sutherland MK, Yu C, Walter RB, Westendorf L, Valliere-Douglass J, Pan L, Cronkite A, Sussman D, Klussman K, Ulrich M, Anderson ME, Stone IJ, Zeng W, Jonas M, Lewis TS, Goswami M, Wang SA, Senter PD, Law CL, Feldman EJ, Benjamin DR. Characterization of SGN-CD123A, A Potent CD123-Directed Antibody-Drug Conjugate for Acute Myeloid Leukemia. Mol Cancer Ther. 2018 Feb;17(2):554-564. doi: 10.1158/1535-7163.MCT-17-0742. Epub 2017 Nov 15.