AB8939 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia, in Relapse, Myelodysplastic Syndrome Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: AB8939
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, multi-centre, non-randomized, 2-part study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AB8939<br>AB8939 administered as a single agent | Drug: AB8939<br>* Intravenous injection (from an initial dose of 0.9 mg/m²)<br>|
| Experimental: AB8939 plus azacitidine<br>AB8939 administered in combination with azacitidine | Drug: AB8939<br>* Intravenous injection (from an initial dose of 0.9 mg/m²)<br>Drug: Azacitidine<br>* Subcutaneous injection (75 mg/m²)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of dose limiting toxicity (DLT) | Identification of the Maximal Tolerated Dose for different dosing schedules | Up to 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The proportion of patients who have a partial or complete response to therapy | Up to 56 days |