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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation and Expansion | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CG-806 | Drug | 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. |
|
| 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) |
| 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) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rafael Bejar, MD, PhD | Aptose Biosciences Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope National Medical Center | Duarte | California | 91010 | United States | ||
| University of Southern California |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38871487 | Derived | Yu G, Zhang W, Basyal M, Nishida Y, Mizumo H, Ly C, Zhang H, Rice WG, Andreeff M. The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and aurora kinases. Leuk Lymphoma. 2024 Nov;65(11):1659-1674. doi: 10.1080/10428194.2024.2364839. Epub 2024 Jun 13. | |
| 36865133 | Derived |
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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) |
| Los Angeles |
| California |
| 90033 |
| United States |
| University of Miami | Miami | Florida | 33136 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Ochsner Healthcare | New Orleans | Louisiana | 70121 | United States |
| Atlantic Hematological Oncology Center | Morristown | New Jersey | 07962 | United States |
| Roswell Park Comprehensive Cancer Center | Buffalo | New York | 14263 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| University Hospital of Cleveland | Cleveland | Ohio | 44106 | United States |
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Yu G, Zhang W, Zhang H, Ly C, Basyal M, Rice WG, Andreeff M. The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases. Res Sq [Preprint]. 2023 Feb 22:rs.3.rs-2570204. doi: 10.21203/rs.3.rs-2570204/v1. |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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