Clinical trial NCT05211570: AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia Refractory
Acute Myeloid Leukemia, in Relapse
Myelodysplastic Syndrome Acute Myeloid Leukemia
Lead sponsor: AB Science
Sponsor class: INDUSTRY
First posted: 2022-01-27
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open-label, multi-centre, non-randomized, 2-part study
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of dose limiting toxicity (DLT)
timeFrame: Up to 56 days
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 56 days
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone marrow Transplantation Unit
city: Alicante
country: Spain
facility: General University Hospital of Alicantet (Hospital General Universitario Dr. Balmis de Alicante)
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Quirónsalud
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Sevilla
country: Spain
facility: Virgen del Rocío University Hospital (Hospital Universitario Virgen del Rocío)
Study officials:
affiliation: Institut Paoli Calmettes, Marseille, France
name: Norbert Vey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Anderson Cancer Center, Houston, Texas
name: Nicholas Short, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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
citation: 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