A Study of CG-806 in Patients With Relapsed or Refractory AML or Higher-Risk MDS

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1a/b Trial of CG-806 in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04477291
• Other study ID #: APTO-CG-806-03
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 6, 2020
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Aptose Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: December 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• CG-806
CG-806 will be given orally in ascending doses starting at 450 mg PO BID until the maximum tolerated dose or candidate recommended Phase 2 dose is reached.

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	University Hospital of Cleveland	Cleveland	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Atlantic Hematological Oncology Center	Morristown	New Jersey
United States	Ochsner Healthcare	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Aptose Biosciences Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events of CG-806	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.	At the end of Cycle 1 (each cycle is 28 days)
Primary	Establish a CG-806 dose that maintains a biologically active plasma concentration	To determine the dose of CG-806 given orally every 12 hours daily that maintains a biologically active plasma concentration during 28-day cycles.	At the end of Cycle 1 (each cycle is 28 days)
Primary	Establish a recommended dose for future development of CG-806	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.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including maximum plasma concentration (Cmax).	Pharmacokinetics variables including maximum plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including minimum plasma concentration (Cmin)	Pharmacokinetics variables including minimum plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including area under the curve (AUC)	Pharmacokinetics variables including plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including volume of distribution	Pharmacokinetics variables including plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including clearance	Pharmacokinetics variables including plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics variables including plasma half-life.	Pharmacokinetics variables including plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect.	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)
Secondary	To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations	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.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	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.	Compare G1 to G3 pharmacokinetics variables including maximum plasma concentration (Cmax)	At the end of Cycle 1 (each cycle is 28 days)
Secondary	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.	Compare G1 to G3 Pharmacokinetics variables including minimum plasma concentration (Cmin)	At the end of Cycle 1 (each cycle is 28 days)
Secondary	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.	Compare G1 to G3 Pharmacokinetics variables including area under the curve (AUC)	At the end of Cycle 1 (each cycle is 28 days)
Secondary	To determine the Relative Bioavailability of Generation 3 formulation given to up to 18	Compare G1 to G3 Pharmacokinetics variables including volume of distribution	At the end of Cycle 1 (each cycle is 28 days)
Secondary	To determine the Relative Bioavailability of Generation 3 formulation given to up to 18	Compare G1 to G3 Pharmacokinetics variables including clearance	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Compare G1 to G3 Pharmacokinetics variables including clearance	Compare G1 to G3 Pharmacokinetics variables including plasma half-life.	At the end of Cycle 1 (each cycle is 28 days)