Clinical trial NCT04477291: A Study of CG-806 in Patients With Relapsed or Refractory AML or Higher-Risk MDS
Official title: A Phase 1a/b Trial of CG-806 in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Keywords: CG-806
Aptose
FLT3
FLT3-ITD
D835Y
F691L
BTK
C481S
TP53
NRAS
IDH1
BCL2
Gilteritinib
Quizartinib
Midostaurin
Crenolanib
Venetoclax
Ibrutinib
Acalabrutinib
Zanubrutinib
LOXO-305
ARQ 531
AML
Acute Myeloid Leukemia
MDS
Myelodysplastic Syndrome
CLL
Chronic Lymphocytic Leukemia
Resistant
Refractory
Relapsed
Intolerant
Kinase Inhibitor
Non covalent
Luxeptinib
Lead sponsor: Aptose Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is being done to evaluate the safety, tolerability and antitumor activity of oral CG-806 (luxeptinib) for the treatment of patients with Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS, whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation.

Detailed description: This is a multicenter, open-label, Phase 1 a/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation. This is to be followed by a cohort expansion phase.

Eligibility criteria: Key Inclusion Criteria:

* Age ≥18 years
* Life expectancy of at least 3 months
* ECOG Performance Status ≤ 2
* Patients must be able to swallow capsules
* Adequate hematologic parameters, unless cytopenias are disease caused
* Adequate renal, liver and cardiac functions

Key Exclusion Criteria:

* Patients with GVHD requiring systemic immunosuppressive therapy
* Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinically significant disease related metabolic disorder
* Clinically significant leukostasis
* Treatment with other investigational drugs or receipt of cytotoxic therapy within 14 days prior to first study treatment administration
* Receipt of cellular immunotherapeutic agents within 4 weeks prior to first study treatment administration

Primary outcomes:
measure: Incidence of treatment-emergent adverse events of CG-806
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Establish a CG-806 dose that maintains a biologically active plasma concentration
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Establish a recommended dose for future development of CG-806
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Pharmacokinetics variables including maximum plasma concentration (Cmax).
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Pharmacokinetics variables including minimum plasma concentration (Cmin)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Pharmacokinetics variables including area under the curve (AUC)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Pharmacokinetics variables including volume of distribution
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Pharmacokinetics variables including clearance
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Pharmacokinetics variables including plasma half-life.
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect.
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 patients on Cycle 1 Day -3 compared to Generation 1 formulation of study drug given to patients during Cycle 1.
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 patients on Cycle 1 Day -3 compared to Generation 1 formulation of study drug given to patients during Cycle 1.
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 patients on Cycle 1 Day -3 compared to Generation 1 formulation of study drug given to patients during Cycle 1.
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the Relative Bioavailability of Generation 3 formulation given to up to 18
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: To determine the Relative Bioavailability of Generation 3 formulation given to up to 18
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Compare G1 to G3 Pharmacokinetics variables including clearance
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Healthcare
state: Louisiana
city: Morristown
country: United States
facility: Atlantic Hematological Oncology Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Aptose Biosciences Inc.
name: Rafael Bejar, MD, PhD
role: STUDY_DIRECTOR
References: