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

Sponsor

CSL Limited (Industry)

Overall Status

Completed

CT.gov ID

NCT01632852

Collaborator

Parexel (Industry)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Biological: CSL362	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Aug 1, 2015

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center of Northwestern University Medical School	Chicago	Illinois	United States	60611
2	Sidney Kimmel Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287
3	Weill Cornell Medical College	New York	New York	United States	10065
4	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
5	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050

Sponsors and Collaborators

CSL Limited
Parexel

Investigators

Study Director: Dr. Mark DeWitte, CSL Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

CSL Limited

ClinicalTrials.gov Identifier:

NCT01632852

Other Study ID Numbers:

CSLCT-AML-11-73

First Posted:

Jul 3, 2012

Last Update Posted:

Oct 9, 2015

Last Verified:

Oct 1, 2015

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Study Results

No Results Posted as of Oct 9, 2015