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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CG-806
Sponsored by
Aptose Biosciences Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring CG-806, Aptose, FLT3, FLT3-ITD, D835Y, F691L, BTK, C481S, TP53, NRAS, IDH1, BCL2, Gilteritinib, Quizartinib, Midostaurin, Crenolanib, Venetoclax, Ibrutinib, Acalabrutinib, Zanubrutinib, LOXO-305, ARQ 531, AML, Acute Myeloid Leukemia, MDS, Myelodysplastic Syndrome, CLL, Chronic Lymphocytic Leukemia, Resistant, Refractory, Relapsed, Intolerant, Kinase Inhibitor, Non covalent, Luxeptinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • City of Hope National Medical CenterRecruiting
  • St Joseph Heritage Healthcare
  • University of Southern CaliforniaRecruiting
  • University of MiamiRecruiting
  • Northwestern UniversityRecruiting
  • Ochsner HealthcareRecruiting
  • Atlantic Hematological Oncology CenterRecruiting
  • Roswell Park Comprehensive Cancer Center
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • University Hospital of ClevelandRecruiting
  • University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation and Expansion

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Pharmacokinetics variables including maximum plasma concentration (Cmax).
Pharmacokinetics variables including maximum plasma concentration at various timepoints.
Pharmacokinetics variables including minimum plasma concentration (Cmin)
Pharmacokinetics variables including minimum plasma concentration at various timepoints.
Pharmacokinetics variables including area under the curve (AUC)
Pharmacokinetics variables including plasma concentration at various timepoints.
Pharmacokinetics variables including volume of distribution
Pharmacokinetics variables including plasma concentration at various timepoints.
Pharmacokinetics variables including clearance
Pharmacokinetics variables including plasma concentration at various timepoints.
Pharmacokinetics variables including plasma half-life.
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.
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
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.
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.
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.
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
Compare G1 to G3 Pharmacokinetics variables including volume of distribution
To determine the Relative Bioavailability of Generation 3 formulation given to up to 18
Compare G1 to G3 Pharmacokinetics variables including clearance
Compare G1 to G3 Pharmacokinetics variables including clearance
Compare G1 to G3 Pharmacokinetics variables including plasma half-life.

Full Information

First Posted
July 13, 2020
Last Updated
June 20, 2023
Sponsor
Aptose Biosciences Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04477291
Brief Title
A Study of CG-806 in Patients With Relapsed or Refractory AML or Higher-Risk MDS
Official Title
A Phase 1a/b Trial of CG-806 in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2020 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aptose Biosciences Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Keywords
CG-806, Aptose, FLT3, FLT3-ITD, D835Y, F691L, BTK, C481S, TP53, NRAS, IDH1, BCL2, Gilteritinib, Quizartinib, Midostaurin, Crenolanib, Venetoclax, Ibrutinib, Acalabrutinib, Zanubrutinib, LOXO-305, ARQ 531, AML, Acute Myeloid Leukemia, MDS, Myelodysplastic Syndrome, CLL, Chronic Lymphocytic Leukemia, Resistant, Refractory, Relapsed, Intolerant, Kinase Inhibitor, Non covalent, Luxeptinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation and Expansion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CG-806
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events of CG-806
Description
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)
Title
Establish a CG-806 dose that maintains a biologically active plasma concentration
Description
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)
Title
Establish a recommended dose for future development of CG-806
Description
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 Outcome Measure Information:
Title
Pharmacokinetics variables including maximum plasma concentration (Cmax).
Description
Pharmacokinetics variables including maximum plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Pharmacokinetics variables including minimum plasma concentration (Cmin)
Description
Pharmacokinetics variables including minimum plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Pharmacokinetics variables including area under the curve (AUC)
Description
Pharmacokinetics variables including plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Pharmacokinetics variables including volume of distribution
Description
Pharmacokinetics variables including plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Pharmacokinetics variables including clearance
Description
Pharmacokinetics variables including plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Pharmacokinetics variables including plasma half-life.
Description
Pharmacokinetics variables including plasma concentration at various timepoints.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect.
Description
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)
Title
To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations
Description
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)
Title
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.
Description
Compare G1 to G3 pharmacokinetics variables including maximum plasma concentration (Cmax)
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
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.
Description
Compare G1 to G3 Pharmacokinetics variables including minimum plasma concentration (Cmin)
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
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.
Description
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)
Title
To determine the Relative Bioavailability of Generation 3 formulation given to up to 18
Description
Compare G1 to G3 Pharmacokinetics variables including volume of distribution
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
To determine the Relative Bioavailability of Generation 3 formulation given to up to 18
Description
Compare G1 to G3 Pharmacokinetics variables including clearance
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Compare G1 to G3 Pharmacokinetics variables including clearance
Description
Compare G1 to G3 Pharmacokinetics variables including plasma half-life.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nawazish Khan, MD, MS
Phone
858-275-6359
Email
nkhan@aptose.com
First Name & Middle Initial & Last Name or Official Title & Degree
Rafael Bejar, MD, PhD
Phone
858-401-6852
Email
rbejar@aptose.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rafael Bejar, MD, PhD
Organizational Affiliation
Aptose Biosciences Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rochelle Hernandez
Phone
626-218-0247
Email
rochernandez@coh.org
First Name & Middle Initial & Last Name & Degree
Paul Koller, MD
Facility Name
St Joseph Heritage Healthcare
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Duran
Email
duran_c@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Eric L Tam, MD
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Posada
Email
jxp2320@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Namrata Chandhok, MD
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophia Rollyson
Phone
312-695-8128
Email
sophia.rollyson@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Jessica Altman, MD
Facility Name
Ochsner Healthcare
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Santos
Phone
504-703-2652
Email
Natalie.santos@ochsner.org
First Name & Middle Initial & Last Name & Degree
Michelle Schmidt
Phone
504-842-6097
Email
michelle.schmidt@ochsner.org
First Name & Middle Initial & Last Name & Degree
Laura Finn, MD
Facility Name
Atlantic Hematological Oncology Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salome Geene
Phone
973-971-6373
Email
salome.geene@atlantichealth.org
First Name & Middle Initial & Last Name & Degree
Amanda Hall
Phone
973-971-5235
Email
AmandaMaria.Hall@atlantichealth.org
First Name & Middle Initial & Last Name & Degree
Mohamad Cherry, MD
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naa-Akomaah Yeboah
Email
yeboahn1@mskcc.org
First Name & Middle Initial & Last Name & Degree
Michelle Gianvito
Email
gianvitm@mskcc.org
First Name & Middle Initial & Last Name & Degree
Aaron Goldberg, MD
Facility Name
University Hospital of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Golwitzer
Phone
216-286-0112
Email
Sarah.Gollwitzer@UHhospitals.org
First Name & Middle Initial & Last Name & Degree
Susan Ackerman
Phone
216-286-4150
Email
susan.ackerman2@uhhospitals.org
First Name & Middle Initial & Last Name & Degree
Benjamin Tomlinson, MD
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julio Guerrero
Phone
713-745-6771
Email
jaguerrero@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Maro Ohanian, DO

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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