AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia, in Relapse Clinical Trial

Official title:

A Phase 1/2 Study to Assess the Safety, Pharmacokinetics, and Efficacy of Daily Intravenous AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05211570
• Other study ID #: AB18001
• Secondary ID: 2020-005122-28
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2022
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: AB Science
• Contact: Clinical Study Coordinator
• Phone: +33(0)147200014
• Email: clinical[@]ab-science.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to define the safety and tolerability of AB8939 in patients with AML by determining the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose for dose expansion study.

Description:

This is a Phase 1/2, open-label, multi-center, non-randomized, 2-part study in patients with refractory and relapsed AML and refractory myelodysplastic syndrome. Study AB18001 has a multi-stage design. The first part is a dose escalation study that aims to determine the safety, tolerability and pharmacokinetic profiles of consecutive daily intravenous administration of AB8939 in patients with refractory or relapsed AML or patients with refractory myelodysplastic syndrome, and to determine the recommended dose for the second-stage dose expansion study. This dose expansion study aims to determine the schedule for a Phase 2 trial in patients with relapsed/refractory AML and to also provide an early efficacy assessment of AB8939.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DOSE ESCALATION STUDY

Key Inclusion Criteria:

• Patients with documented diagnosis of acute myeloid leukemia (AML) based on the last version of the World Health Organization classification and eligible to second or third line of treatment.
• Patients with documented diagnosis of refractory melyodisplastic syndrome in second or third line of treatment, and with high risk at prognosis based on the IPSS-R scoring system.
• ECOG performance status = 1
• Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
• Patients are able and willing to comply with study procedures as per protocol, including bone marrow biopsies

Key Exclusion Criteria:

• Patients eligible to a standard of care
• Patients eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
• Patients diagnosed with acute promyelocytic leukemia (M3)
• Patients with clinically active CNS leukemia
• Patients with HSCT within 100 days prior to the first administration of AB8939
• Women who are lactating/breastfeeding or who plan to breastfeed while on study
• Women with a positive pregnancy test Other protocol-defined inclusion/exclusion criteria may apply EXPANSION COHORT STUDY

Key Inclusion Criteria:

• Patients with documented diagnosis of acute myeloid leukemia (AML) based on the last version of the World Health Organization classification and eligible to second or third line of treatment.
• ECOG performance status = 2
• Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
• Patients are able and willing to comply with study procedures as per protocol, including bone marrow biopsies

Key Exclusion Criteria:

• Patients eligible to a standard of care
• Patients eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
• Patients diagnosed with acute promyelocytic leukemia (M3)
• Patients with clinically active CNS leukemia
• Patients with HSCT within 100 days prior to the first administration of AB8939
• Women who are lactating/breastfeeding or who plan to breastfeed while on study
• Women with a positive pregnancy test Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Acute Myeloid Leukemia, in Relapse
• GATA2 Deficiency
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Intervention

Drug:
• AB8939
Intravenous injection (from an initial dose of 0.9 mg/m²)
• Azacitidine
Subcutaneous injection (75 mg/m²)

Locations

Country	Name	City	State
France	Institut Paoli Calmettes	Marseille
Greece	National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone marrow Transplantation Unit	Athens
Spain	General University Hospital of Alicantet (Hospital General Universitario Dr. Balmis de Alicante)	Alicante
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Quirónsalud	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Virgen del Rocío University Hospital (Hospital Universitario Virgen del Rocío)	Sevilla
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

United States,  France,  Greece,  Spain, 

References & Publications (3)

Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. AB8939, a Microtubule-Destabilizing Agent with Potential to Overcome Multidrug Resistance, is Active Across the Range (M0-M7) of Acute Myeloid Leukemia Subtypes. Blood (2019) 134 (Supplement_1): 5154. doi.org/10.1182/blood-2019-127021

Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-derived Xenograft Models of Acute Myeloid Leukemia. Blood (2019) 134 (Supplement_1): 5142. doi.org/10.1182/blood-2019-127143

Humbert M, Goubard A, Mansfield C, Hermine O, Dubreuil P, et al. Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood (2019) 134 (Supplement_1): 2075. doi.org/10.1182/blood-2019-122540

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose limiting toxicity (DLT)	Identification of the Maximal Tolerated Dose for different dosing schedules	Up to 56 days
Secondary	Objective Response Rate	The proportion of patients who have a partial or complete response to therapy	Up to 56 days