AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory; Myelodysplastic Syndrome Acute Myeloid Leukemia
• Intervention / Treatment: Drug: AB8939; Drug: Venetoclax

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Study Coordinator; Phone Number: +33(0)147200014; Email: clinical@ab-science.com

Study Locations

• France
  • Marseille, France
    • Not yet recruiting
    • Institut Paoli Calmettes
• Greece
  • Athens, Greece
    • Recruiting
    • National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone marrow Transplantation Unit
• Spain
  • Alicante, Spain
    • Recruiting
    • General University Hospital of Alicantet (Hospital General Universitario Dr. Balmis de Alicante)
  • Cáceres, Spain
    • Recruiting
    • Hospital San Pedro De Alcantara
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • MD Anderson Cancer Center Madrid
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Quirónsalud
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra
  • Seville, Spain
    • Recruiting
    • Virgen del Rocío University Hospital (Hospital Universitario Virgen del Rocío)
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AB8939; AB8939 administered as a single agent	Drug: AB8939; Intravenous injection (from an initial dose of 0.9 mg/m²)
Experimental: AB8939 plus Venetoclax; AB8939 administered in combination with venetoclax	Drug: AB8939; Intravenous injection (from an initial dose of 0.9 mg/m²); Drug: Venetoclax; the recommended starting dose for AML indication is 100 mg. Dose escalating regimen as per SmPC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of dose limiting toxicity (DLT)	Identification of the Maximal Tolerated Dose for different dosing schedules	Up to 56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The proportion of patients who have a partial or complete response to therapy	Up to 56 days

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Norbert Vey, MD, Institut Paoli Calmettes, Marseille, France; Principal Investigator: Nicholas Short, MD, MD Anderson Cancer Center, Houston, Texas

Publications and helpful links

General Publications

• 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
• 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
• 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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myelodysplastic Syndromes; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; GATA2 Deficiency; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; venetoclax
• Other Study ID Numbers: AB18001; 2020-005122-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No