Back to resultsAPR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
Primary Purpose
MDS, Myelodysplastic Syndromes
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
APR-548 + Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for MDS
Eligibility Criteria
Inclusion Criteria:
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
Adequate organ function as defined by the following laboratory values:
- Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
- Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
- Age ≥18 years at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
- Projected life expectancy of ≥12 weeks.
- Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.
Exclusion Criteria:
Cardiac abnormalities, which includes, but not limited to:
- Myocardial infarction within six months prior to enrollment
- New York Heart Association Class III or IV heart failure or known LVEF <40%
- Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
- Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
- Prior exposure to eprenetapopt (APR-246).
- A female subject who is pregnant or breast-feeding.
- Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
- Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
- Known history or current evidence of ocular disease in either eye
Sites / Locations
- H. Lee Moffitt Cancer Center
- Massachusetts General Hospital
- Dana Farber Cancer Institue
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
Dose level 1
Dose level 2
Dose level 3
Outcomes
Primary Outcome Measures
To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine.
Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04638309
Brief Title
APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
Official Title
Phase 1 Study to Evaluate Safety and Efficacy of APR-548 in Combination With Azacitidine for the Treatment of TP53-Mutant Myelodysplastic Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
September 20, 2021 (Actual)
Primary Completion Date
April 25, 2022 (Actual)
Study Completion Date
April 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aprea Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.
Detailed Description
Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MDS, Myelodysplastic Syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Dose level 1
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Dose level 2
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Dose level 3
Intervention Type
Drug
Intervention Name(s)
APR-548 + Azacitidine
Intervention Description
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Primary Outcome Measure Information:
Title
To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine.
Description
Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.
Time Frame
Through study completion, approximately 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated, written informed consent prior to any study specific procedures.
Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
Adequate organ function as defined by the following laboratory values:
Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
Age ≥18 years at the time of signing the informed consent form.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
Projected life expectancy of ≥12 weeks.
Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.
Exclusion Criteria:
Cardiac abnormalities, which includes, but not limited to:
Myocardial infarction within six months prior to enrollment
New York Heart Association Class III or IV heart failure or known LVEF <40%
Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
Prior exposure to eprenetapopt (APR-246).
A female subject who is pregnant or breast-feeding.
Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
Known history or current evidence of ocular disease in either eye
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joachim Gullbo, MD
Organizational Affiliation
Theradex Oncology
Official's Role
Study Director
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institue
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
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