AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Sponsor

AB Science (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05211570

Collaborator

(none)

Enrollment

Locations

Arms

12.9

Anticipated Duration (Months)

15.6

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia, in Relapse Myelodysplastic Syndrome Acute Myeloid Leukemia	Drug: AB8939 Drug: Azacitidine	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

78 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Open-label, multi-centre, non-randomized, 2-part studyOpen-label, multi-centre, non-randomized, 2-part study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

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 azacitidine AB8939 administered in combination with azacitidine	Drug: AB8939 Intravenous injection (from an initial dose of 0.9 mg/m²) Drug: Azacitidine Subcutaneous injection (75 mg/m²)

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 azacitidine

AB8939 administered in combination with azacitidine

Drug: AB8939

Intravenous injection (from an initial dose of 0.9 mg/m²)

Drug: Azacitidine

Subcutaneous injection (75 mg/m²)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Objective Response Rate [Up to 56 days]
The proportion of patients who have a partial or complete response to therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MD Anderson Cancer Center	Houston	Texas	United States	77030
2	Institut Paoli Calmettes	Marseille		France
3	Hospital Universitario 12 de Octubre	Madrid		Spain
4	Hospital Universitario Quirónsalud	Madrid		Spain
5	Clínica Universidad de Navarra	Pamplona		Spain

Sponsors and Collaborators

AB Science

Investigators

Principal Investigator: Norbert Vey, MD, Institut Paoli Calmettes, Marseille, France
Principal Investigator: Nicholas Short, MD, MD Anderson Cancer Center, Houston, Texas