Back to resultsStudy of KHK2823 in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndrome
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
KHK2823
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
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
Sites / Locations
- University of Sussex, Royal Sussex County Hospital
- Beatson West of Scotland Cancer Centre
- St James's Institute of Oncology
- NIHR/Wellcome UCLH Clinical Research Facility University College Hospital London
- St Bartholomew's Hospital
- Northern Centre for Cancer Care, Freeman Road Hospital
- Southampton General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
KHK2823
Arm Description
single agent KHK2823 administered at selected dose levels
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
Secondary Outcome Measures
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)
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)
Immunogenicity: anti-KHK2823 antibody
Measure of human anti-drug antibody
Pharmacodynamics: CD123+
Measure of KHK2823 target expression
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02181699
Brief Title
Study of KHK2823 in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Official Title
Phase 1 Study of KHK2823 in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
Failed treatment response
Study Start Date
June 2014 (Actual)
Primary Completion Date
May 10, 2019 (Actual)
Study Completion Date
May 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Kirin, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KHK2823
Arm Type
Experimental
Arm Description
single agent KHK2823 administered at selected dose levels
Intervention Type
Drug
Intervention Name(s)
KHK2823
Intervention Description
single agent KHK2823
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
Time Frame
Assessed weekly for duration of treatment (anticipated minimum 8 weeks), plus 42 day follow up period
Secondary Outcome Measure Information:
Title
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)
Time Frame
Assessed during first 24 weeks of treatment, plus 42 day follow up period
Title
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)
Time Frame
Assessed every 8 weeks for duration of treatment (anticipated minimum 8 weeks), plus 14 day follow up period
Title
Immunogenicity: anti-KHK2823 antibody
Description
Measure of human anti-drug antibody
Time Frame
Assessed every 4 weeks for first 24 weeks of treatment, plus 42 day follow up period
Title
Pharmacodynamics: CD123+
Description
Measure of KHK2823 target expression
Time Frame
Assessed during first 24 weeks of treatment, plus 42 day follow up period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Sussex, Royal Sussex County Hospital
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Facility Name
St James's Institute of Oncology
City
Leeds
Country
United Kingdom
Facility Name
NIHR/Wellcome UCLH Clinical Research Facility University College Hospital London
City
London
Country
United Kingdom
Facility Name
St Bartholomew's Hospital
City
London
Country
United Kingdom
Facility Name
Northern Centre for Cancer Care, Freeman Road Hospital
City
Newcastle Upon Tyne
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Study of KHK2823 in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
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