Study of KHK2823 in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Phase 1 Study of KHK2823 in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome.

This is a first in human, non-randomized, open-label, dose escalation study to investigate the safety, pharmacokinetics, immunogenicity and pharmacodynamics of repeat doses of KHK2823.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: KHK2823

Detailed Description

This is a Phase 1, multi-center, open-label, dose-escalation study of KHK2823 in adult patients with previously untreated AML who are not candidates for intensive remission induction therapy; relapsed/refractory AML for whom no other standard therapy is available or appropriate; or relapsed/refractory MDS who have received prior therapy with a hypomethylating agent, such as decitabine and azacitidine or who are not candidates to receive a hypomethylating agent, this would include high risk or transfusion-dependent low risk patients. Patients must have documented primary or secondary AML or MDS according to World Health Organization (WHO) criteria. Following the provision of signed informed consent, patients will be screened for entry into the study. The study consists of 2 parts. In Part 1, 3 to 6 patients per cohort will be enrolled sequentially in up to 7 dose-escalation cohorts to establish the MTD. KHK2823 will be administered once weekly. In Part 2, up to an additional 18 patients may be enrolled to further evaluate the safety, PK, PD, potential anti-leukemic activity of KHK2823.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • University of Sussex, Royal Sussex County Hospital
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom
    • St James's Institute of Oncology
  • London, United Kingdom
    • St Bartholomew's Hospital
  • London, United Kingdom
    • NIHR/Wellcome UCLH Clinical Research Facility University College Hospital London
  • Newcastle Upon Tyne, United Kingdom
    • Northern Centre for Cancer Care, Freeman Road Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females ≥ 18 years old with previously untreated AML who are not candidates for intensive remission induction therapy; relapsed/refractory AML for whom no other standard therapy is available or appropriate; or relapsed/refractory MDS who have received prior therapy with a hypomethylating agent or who are not candidates to receive a hypomethylating agent
• Histopathologically/cytologically documented primary or secondary AML, as defined by WHO criteria, or MDS, confirmed by pathology review at treating institution
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
• Life expectancy of at least 3 months

Exclusion Criteria:

• Histological diagnosis of acute promyelocytic leukemia (FAB Type M3)
• Clinically significant central nervous system leukemia
• Treatment of the underlying hematologic condition with systemic therapy during the treatment period, including any chemotherapy, radiation or investigational therapy, within 2 weeks prior to KHK2823 administration; or immunotherapy within 30 days prior to KHK2823 administration; with the exception of hydroxyurea (Hydrea®) for treatment of hyperleukocytosis, which must be discontinued at least 24 hours prior to the first dose of KHK2823

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: KHK2823; single agent KHK2823 administered at selected dose levels	Drug: KHK2823; single agent KHK2823

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.	Assessed weekly for duration of treatment (anticipated minimum 8 weeks), plus 42 day follow up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Peak serum concentration (Cmax) Time to reach Cmax (tmax) Minimum serum concentration (Ctrough) Area under curve (AUC) Half-life (t1/2) Clearance (CL) Volume of distribution (Vd) Accumulation ratio (R)		Assessed during first 24 weeks of treatment, plus 42 day follow up period
Disease Response: overall response rate (ORR), overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DFS)		Assessed every 8 weeks for duration of treatment (anticipated minimum 8 weeks), plus 14 day follow up period
Immunogenicity: anti-KHK2823 antibody	Measure of human anti-drug antibody	Assessed every 4 weeks for first 24 weeks of treatment, plus 42 day follow up period
Pharmacodynamics: CD123+	Measure of KHK2823 target expression	Assessed during first 24 weeks of treatment, plus 42 day follow up period

Collaborators and Investigators

• Sponsor: Kyowa Kirin, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): May 10, 2019
• Study Completion (Actual): May 10, 2019

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: July 3, 2014
• First Posted (Estimated): July 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: 2823-001; 2013-003657-21 (EudraCT Number)