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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Biological: CSL362

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University Medical School
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Cancer Center at Johns Hopkins
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CSL362; See Intervention Description

Biological: CSL362; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSL Limited
• Collaborators: Parexel
• Investigators: Study Director: Dr. Mark DeWitte, CSL Limited

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 29, 2012
• First Submitted That Met QC Criteria: June 29, 2012
• First Posted (Estimate): July 3, 2012

Study Record Updates

• Last Update Posted (Estimate): October 9, 2015
• Last Update Submitted That Met QC Criteria: October 8, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CSLCT-AML-11-73