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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Drug: CG-806

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Healthcare
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Atlantic Hematological Oncology Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital of Cleveland
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion; 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
Pharmacokinetics variables including clearance	Pharmacokinetics variables including plasma concentration at various timepoints.	At the end of Cycle 1 (each cycle is 28 days)
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)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Aptose Biosciences Inc.
• Investigators: Study Director: Rafael Bejar, MD, PhD, Aptose Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): April 15, 2024

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Relapsed; Refractory; AML; Ibrutinib; MDS; Venetoclax; CLL; TP53; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; IDH1; BTK; CG-806; Aptose; FLT3; FLT3-ITD; D835Y; F691L; C481S; NRAS; BCL2; Gilteritinib; Quizartinib; Midostaurin; Crenolanib; Acalabrutinib; Zanubrutinib; LOXO-305; ARQ 531; Resistant; Intolerant; Kinase Inhibitor; Non covalent; Luxeptinib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
• Other Study ID Numbers: APTO-CG-806-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No