AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: AB8939, Venetoclax.
- Who it may be relevant to
- Registry conditions: Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia, in Relapse, Myelodysplastic Syndrome Acute Myeloid Leukemia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, France, Greece, Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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
Overview
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.
Interventions
- 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.
Primary outcome measures
- Rate of dose limiting toxicity (DLT) [Time frame: Up to 56 days]
Secondary outcome measures (1)
- Objective Response Rate [Time frame: Up to 56 days]
Eligibility criteria
DOSE ESCALATION STUDY
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
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
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
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Spain · 7 centers
- General University Hospital of Alicantet (Hospital General Universitario Dr. Balmis de Ali — Alicante
- Hospital San Pedro de Alcantara — Cáceres
- Hospital Universitario 12 de Octubre — Madrid
- Hospital Universitario Quirónsalud — Madrid
- MD Anderson Cancer Center Madrid — Madrid
- Clínica Universidad de Navarra — Pamplona
- Virgen del Rocío University Hospital (Hospital Universitario Virgen del Rocío) — Seville
United States · 1 center
- MD Anderson Cancer Center — Houston
France · 1 center
- Institut Paoli Calmettes — Marseille
Greece · 1 center
- National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone ma — Athens
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
Identifiers
NCT: NCT05211570 · AB18001 · 2020-005122-28