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

Phase 1TerminatedNCT04477291

Aptose Biosciences Inc.45 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes

Interventions

CG-806DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

City of Hope National Medical Center

Duarte, California, United States

University of Southern California

Los Angeles, California, United States

University of Miami

Miami, Florida, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes

Pharmacokinetics variables including maximum plasma concentration (Cmax).

Pharmacokinetics variables including maximum plasma concentration at various timepoints.

Time frame: 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.

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Pharmacokinetics variables including area under the curve (AUC)

Data from ClinicalTrials.gov

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Northwestern University

Chicago, Illinois, United States

Ochsner Healthcare

New Orleans, Louisiana, United States

Atlantic Hematological Oncology Center

Morristown, New Jersey, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University Hospital of Cleveland

Cleveland, Ohio, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Pharmacokinetics variables including plasma concentration at various timepoints.

Time frame: 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.

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Pharmacokinetics variables including clearance

Pharmacokinetics variables including plasma concentration at various timepoints.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: At the end of Cycle 1 (each cycle is 28 days)