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

NCT04477291 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: APTO-CG-806-03
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 10

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (14)

• Pharmacokinetics variables including maximum plasma concentration (Cmax).

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

• Pharmacokinetics variables including minimum plasma concentration (Cmin)

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

• Pharmacokinetics variables including area under the curve (AUC)

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

• Pharmacokinetics variables including volume of distribution

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

• Pharmacokinetics variables including clearance

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

Study Arms (1)

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.

Drug: CG-806

Interventions

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.

Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aptose Biosciences Inc.: lead

Study Sites (10)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Ochsner Healthcare

New Orleans, Louisiana, 70121, United States

Location

Atlantic Hematological Oncology Center

Morristown, New Jersey, 07962, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 38871487 DERIVED

• 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.

  PMID: 36865133 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rafael Bejar, MD, PhD

  Aptose Biosciences Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 20, 2020
• Study Start: October 6, 2020
• Primary Completion: April 15, 2024
• Study Completion: April 15, 2024
• Last Updated: March 7, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)