Leukemia, Myeloid, Acute
Conditions
Brief summary
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.
Interventions
BIOLOGICALCSL362
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.
Sponsors
Parexel
CSL Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Adverse Events (AEs) | From the first treatment (Day 1) up to approximately Day 106 | Number of subjects reporting any AEs and the severity of those AEs. |
| Dose-limiting toxicity (DLT) evaluation | From the first treatment (Day 1) up to approximately Day 106 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameters | 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 | 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) |
| Number of subjects developing antibodies against CSL362 | From the first treatment (Day 1) up to approximately Day 106 | — |
Countries
Australia, United States
Outcome results
None listed