A Study of CG-806 in Patients With Relapsed or Refractory AML or Higher-Risk MDS
- Registration Number
- NCT04477291
- Lead Sponsor
- Aptose Biosciences Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 45
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation and Expansion CG-806 Dose Escalation and Expansion; CG-806 will be given orally in ascending doses in patients with relapsed or refractory AML or higher-risk MDS (escalation cohort), until the maximum tolerated dose or candidate recommended Phase 2 dose is reached. Followed up by up to 50 patients enrolled in the expansion cohort at the recommended dose.
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events of CG-806 At the end of Cycle 1 (each cycle is 28 days) Patients will be assessed for adverse events during all cycles of treatment and for dose limiting toxicities in Cycle 1 (28-days). Dose escalation to a higher dose level will be considered if none of the first three patients who complete Cycle 1 (28-days) at a given dose level experience a dose limiting toxicity or if only 1 of 6 patients at a given dose level experience a dose-limiting toxicity.
Establish a CG-806 dose that maintains a biologically active plasma concentration At the end of Cycle 1 (each cycle is 28 days) To determine the dose of CG-806 given orally every 12 hours daily that maintains a biologically active plasma concentration during 28-day cycles.
Establish a recommended dose for future development of CG-806 At the end of Cycle 1 (each cycle is 28 days) To establish the maximum tolerated dose and/or recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with AML and other advanced myeloid malignancies.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics variables including area under the curve (AUC) At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including plasma concentration at various timepoints.
To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect. At the end of Cycle 1 (each cycle is 28 days) To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect.
Compare G1 to G3 Pharmacokinetics variables including clearance At the end of Cycle 1 (each cycle is 28 days) Compare G1 to G3 Pharmacokinetics variables including plasma half-life.
Pharmacokinetics variables including volume of distribution At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including plasma concentration at various timepoints.
Pharmacokinetics variables including clearance At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including plasma concentration at various timepoints.
Pharmacokinetics variables including plasma half-life. At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including plasma concentration at various timepoints.
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. At the end of Cycle 1 (each cycle is 28 days) Compare G1 to G3 Pharmacokinetics variables including area under the curve (AUC)
Pharmacokinetics variables including maximum plasma concentration (Cmax). At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including maximum plasma concentration at various timepoints.
Pharmacokinetics variables including minimum plasma concentration (Cmin) At the end of Cycle 1 (each cycle is 28 days) Pharmacokinetics variables including minimum plasma concentration at various timepoints.
To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations At the end of Cycle 1 (each cycle is 28 days) To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, and FDG PET-CT imaging evaluations.
To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 At the end of Cycle 1 (each cycle is 28 days) Compare G1 to G3 Pharmacokinetics variables including clearance
Trial Locations
- Locations (10)
University of Miami
🇺🇸Miami, Florida, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Ochsner Healthcare
🇺🇸New Orleans, Louisiana, United States
Atlantic Hematological Oncology Center
🇺🇸Morristown, New Jersey, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University Hospital of Cleveland
🇺🇸Cleveland, Ohio, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States