AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат AB8939
  Intravenous injection (from an initial dose of 0.9 mg/m²)
• Препарат Venetoclax
  the recommended starting dose for AML indication is 100 mg. Dose escalating regimen as per SmPC.

Первичные конечные точки

• Rate of dose limiting toxicity (DLT) [Срок оценки: Up to 56 days]

Вторичные конечные точки (1)

• Objective Response Rate [Срок оценки: Up to 56 days]

Критерии участия

DOSE ESCALATION STUDY

Критерии включения

• 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

Критерии исключения

• 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

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 7 центров

• 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

США · 1 центр

• MD Anderson Cancer Center — Houston

Франция · 1 центр

• Institut Paoli Calmettes — Marseille

Греция · 1 центр

• National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone ma — Athens

Публикации

• 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

Идентификаторы

NCT: NCT05211570 · AB18001 · 2020-005122-28

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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