AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia, in Relapse; Myelodysplastic Syndrome Acute Myeloid Leukemia; Acute Myeloid Leukemia Refractory
• Interventions: Drug: AB8939; Drug: Azacitidine

• Registration Number: NCT05211570
• Lead Sponsor: AB Science

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.

Study Timeline

• Study First Submitted: 2022-01-12
• Study First Submitted QC: 2022-01-14
• Study First Posted: 2022-01-27
• Study Start: 2022-06-01
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-06
• Last Update Posted: 2023-10-10
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AB8939 plus azacitidine	Azacitidine	AB8939 administered in combination with azacitidine
AB8939	AB8939	AB8939 administered as a single agent
AB8939 plus azacitidine	AB8939	AB8939 administered in combination with azacitidine

Primary Outcome Measures

Name	Time	Method
Rate of dose limiting toxicity (DLT)	Up to 56 days	Identification of the Maximal Tolerated Dose for different dosing schedules

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	Up to 56 days	The proportion of patients who have a partial or complete response to therapy

Trial Locations

Locations (10)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Clínica Universidad de Navarra; 🇪🇸 Pamplona, Spain

National and Kapodistrian University of Athens NKUA · Department of Hematology and Bone marrow Transplantation Unit; 🇬🇷 Athens, Greece

Institut Paoli Calmettes; 🇫🇷 Marseille, France

General University Hospital of Alicantet (Hospital General Universitario Dr. Balmis de Alicante); 🇪🇸 Alicante, Spain

Hospital San Pedro de Alcantara; 🇪🇸 Cáceres, Spain

MD Anderson Cancer Center Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Quirónsalud; 🇪🇸 Madrid, Spain

Virgen del Rocío University Hospital (Hospital Universitario Virgen del Rocío); 🇪🇸 Sevilla, Spain