A Study of CSL362 in Patients With CD123+ Acute Myeloid Leukemia Currently in Remission

Study Overview
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Brief Summary
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This is a first in human, prospective, multicenter, nonrandomized, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of repeat doses of CSL362.

Official Title
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A Phase 1 Study of CSL362 (Anti-IL3Rα / Anti-CD123 Monoclonal Antibody) in Patients With CD123+ Acute Myeloid Leukemia in Complete Remission or Complete Remission With Incomplete Platelet Recovery at High Risk for Early Relapse

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Biological: CSL362


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 years or older. Previous diagnosis of CD123+ acute myeloid leukemia (AML), de novo or secondary. Completed and recovered from all planned induction and consolidation therapy according to the institution's standard of care, and achieved a complete remission (CR)/CR with incomplete platelet recovery (CRp); either first or second CR. Has factors conferring high risk of relapse. No plans for additional post-remission chemotherapy. Not currently a candidate for allogeneic hematopoietic stem cell transplant (HSCT). Exclusion Criteria: Diagnosis of acute promyelocytic leukemia (APL). Known leukemic involvement of the central nervous system. Life expectancy 4 months or less as estimated by the investigator. Concurrent treatment or planned treatment with other anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL362<br>See Intervention Description | Biological: CSL362<br>* CSL362 is humanized monoclonal antibody that targets the alpha chain of the interleukin 3 receptor (IL3Rα; also known as CD123) and is optimised for enhanced activation of antibody-dependent cell-mediated cytotoxicity (ADCC) via natural killer cells. CSL362 is a sterile solution for injection and will be administered by intravenous infusion to subjects in sequential, escalating dose level cohorts, at doses up to 12.0 mg/kg. CSL362 will be administered every 14 days for a total of 6 infusions per subject. The 6 infusions for each individual subject will contain the same dose of CSL362.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Adverse Events (AEs) | Number of subjects reporting any AEs and the severity of those AEs. | From the first treatment (Day 1) up to approximately Day 106 | 
| Dose-limiting toxicity (DLT) evaluation | Number of participants with DLT. Dose-limiting toxicity (DLT) is defined as: A non-hematological toxicity grade 3 or worse. A hematological toxicity grade 3 that does not recover to baseline within 14 days. A hematological toxicity grade 4 or worse according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.0. | From the first treatment (Day 1) up to approximately Day 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameters | PK Parameters comprise: Area under the serum concentration time curve (AUC) from time point zero (before dosing): to the time point at which the analyte first returns to baseline (AUC0-last) to a meaningful time after infusion (AUC0-y) extrapolated to infinity (AUC0-∞). The maximum observed serum concentration (Cmax). First time to reach maximum concentration in serum (Tmax). Terminal serum half-life (t 1/2) | Before each infusion and: at 6 time points within a week after infusion 1, at 1 time point within a week after infusions 2 to 5, at 5 time points within a week after infusion 6, and once at the final visit, approximately 5 weeks after infusion 6 | 
| Number of subjects developing antibodies against CSL362 |  | From the first treatment (Day 1) up to approximately Day 106 |