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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02181699
• Other study ID #: 2823-001
• Secondary ID: 2013-003657-21
• Status: Terminated
• Phase: Phase 1
• Start date: June 2014
• Est. completion date: May 10, 2019

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: May 10, 2019
• Est. primary completion date: May 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• KHK2823
single agent KHK2823

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kyowa Kirin, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Pharmacodynamics: CD123+	Measure of KHK2823 target expression	Assessed during first 24 weeks of treatment, plus 42 day follow up period