APR-246 in Combination With Azacitidine for TP53 Mutated AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes) Following Allogeneic Stem Cell Transplant

Phase II Trial of APR-246 in Combination With Azacitidine as Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplant

A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT (hematopoietic stem cell transplant) for patients with TP53 mutant AML or MDS.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia or Myelodysplastic Syndromes
• Intervention / Treatment: Drug: APR-246

Detailed Description

A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT for patients with TP53 mutant AML or MDS.

Patients will be prescreened for TP53 mutant AML or MDS before they have a HSCT. In order to proceed with APR-246 and azacitidine treatment, engraftment must be confirmed between Day 30 to Day 100 post-HSCT.

APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21278
      • Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patient must have previously met pre-transplantation eligibility.
2. Patient has received an allogeneic transplant for AML or MDS.
3. Any standard (non-study) conditioning [MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)] will be permitted.
4. Patient is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
5. Patient is in complete remission after the transplant and has achieved engraftment. .
6. Patients who have developed grades II-IV acute GVHD (graft versus host disease) will be allowed to initiate maintenance therapy based on the following criteria:

7. Females must either:

   Be of non-childbearing potential postmenopausal (defined as at least 1 year without menses) prior to screening, or documented as surgically sterilized (e.g., hysterectomy or tubal ligation) at least 1 month prior to the screening visit Or, if of childbearing potential, Agree not to try to become pregnant during the study and for 6 months after the final study drug administration And have a negative serum pregnancy test at screening And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after final study drug administration.

8. Females must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
9. Males (even if surgically sterilized), and their partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period.
10. Males must not donate sperm throughout the study drug treatment period.
11. Agrees not to participate in another interventional study while on treatment.
12. Karnofsky Performance Status 70 or greater is required.

Exclusion Criteria:

1. Prior participation in an APR-246 study.
2. Use of umbilical cord blood donor and stem cell source.
3. Patient has uncontrolled infection.
4. Use of investigational agent within 14 days of pre-HSCT screening or anytime thereafter.
5. Use of hypomethylating agent, cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS or AML within 14 days of the first day of pre-HSCT screening or anytime thereafter.
6. Patient has used experimental therapy for acute GVHD at any time post-transplant.
7. Patient requires treatment with supplemental oxygen not including usage of non-invasive CPAP (continuous positive airways pressure) at night.

8. Patient has any of the following cardiac abnormalities (as determined by treating physician):

   1. Myocardial infarct within six months prior to registration
   2. New York Heart Association Class II or worse heart failure or known LVEF (left ventricular ejection fraction) < the institution LLN (lower limit normal)
   3. A history of familial long QT syndrome
   4. Electrocardiographic evidence of acute ischemia at screening
   5. Symptomatic atrial or ventricular arrhythmias not controlled by medications
   6. QTc ≥ 470 ms calculated from a mean of 3 ECG (electrocardiogram) readings using Fridericia's correction (QTcF = QT/RR0.33)
   7. Bradycardia (<40 bpm) at screening

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: Experimental arm: APR-246 + azacitidine; APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles	Drug: APR-246; APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.; Other Names: Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess Relapse-free Survival (RFS) in Patients With TP53 Mutated AML or MDS After Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT).	Relapse-free survival (RFS) at 12 months or longer if data permits. RFS was defined as the time from HCT to relapse after HCT or death, whichever occurred first.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Aprea Therapeutics
• Investigators: Principal Investigator: Asmita Mishra, MD, PhD, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612

Publications and helpful links

General Publications

• Mishra A, Tamari R, DeZern AE, Byrne MT, Gooptu M, Chen YB, Deeg HJ, Sallman D, Gallacher P, Wennborg A, Hickman DK, Attar EC, Fernandez HF. Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2022 Dec 1;40(34):3985-3993. doi: 10.1200/JCO.22.00181. Epub 2022 Jul 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): August 27, 2021
• Study Completion (Actual): January 14, 2022

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Azacitidine
• Other Study ID Numbers: A19-11172

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No