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

Sponsor

Aptose Biosciences Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04477291

Collaborator

(none)

Enrollment

Locations

Arm

31.8

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes	Drug: CG-806	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 6, 2020

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.
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.
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 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.
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 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 maximum plasma concentration (Cmax)
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 minimum plasma concentration (Cmin)
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)
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 volume of distribution
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
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	St Joseph Heritage Healthcare	Fullerton	California	United States	92835
3	University of Miami	Miami	Florida	United States	33136
4	Northwestern University	Chicago	Illinois	United States	60611
5	Ochsner Healthcare	New Orleans	Louisiana	United States	70121
6	Atlantic Hematological Oncology Center	Morristown	New Jersey	United States	07962
7	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14263
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	University Hospital of Cleveland	Cleveland	Ohio	United States	44106
10	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030