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APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)

Sponsor
Aprea Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT04638309
Collaborator
(none)
4
Enrollment
4
Locations
3
Arms
7.1
Actual Duration (Months)
1
Patient Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: APR-548 + Azacitidine
 Phase 1

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
4 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 20, 2021
Actual Primary Completion Date :
Apr 25, 2022
Actual Study Completion Date :
Apr 25, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Dose level 1

Drug: APR-548 + Azacitidine
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Experimental: Cohort 2

Dose level 2

Drug: APR-548 + Azacitidine
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Experimental: Cohort 3

Dose level 3

Drug: APR-548 + Azacitidine
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine

Outcome Measures

Primary Outcome Measures

  1. To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine. [Through study completion, approximately 1 year]

    Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Provision of signed and dated, written informed consent prior to any study specific procedures.

  2. Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.

  3. Adequate organ function as defined by the following laboratory values:

  4. Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),

  5. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,

  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.

  7. Age ≥18 years at the time of signing the informed consent form.

  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).

  9. Projected life expectancy of ≥12 weeks.

  10. Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.

Exclusion Criteria:

  1. Cardiac abnormalities, which includes, but not limited to:

  2. Myocardial infarction within six months prior to enrollment

  3. New York Heart Association Class III or IV heart failure or known LVEF <40%

  4. Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.

  5. 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.

  6. Prior exposure to eprenetapopt (APR-246).

  7. A female subject who is pregnant or breast-feeding.

  8. Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.

  9. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.

  10. Known history or current evidence of ocular disease in either eye

Contacts and Locations

Locations

Site City State Country Postal Code
1 H. Lee Moffitt Cancer Center Tampa Florida United States 33612
2 Massachusetts General Hospital Boston Massachusetts United States 02114
3 Dana Farber Cancer Institue Boston Massachusetts United States 02215
4 MD Anderson Cancer Center Houston Texas United States 77030

Sponsors and Collaborators

  • Aprea Therapeutics

Investigators

  • Study Director: Joachim Gullbo, MD, Theradex Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Aprea Therapeutics
ClinicalTrials.gov Identifier:
NCT04638309
Other Study ID Numbers:
  • A20-11202
First Posted:
Nov 20, 2020
Last Update Posted:
Jul 22, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Preleukemia
Myelodysplastic Syndromes
Syndrome
Azacitidine

Study Results

No Results Posted as of Jul 22, 2022