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

NCT03931291 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: A19-11172
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Acute Myeloid Leukemia or Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Experimental arm: APR-246 + azacitidine

EXPERIMENTAL

APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles

Drug: APR-246

Interventions

APR-246 DRUG

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.

Also known as: Azacitidine

Experimental arm: APR-246 + azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have previously met pre-transplantation eligibility.
• Patient has received an allogeneic transplant for AML or MDS.
• Any standard (non-study) conditioning \[MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)\] will be permitted.
• Patient is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
• Patient is in complete remission after the transplant and has achieved engraftment. .
• 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:
• 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.
• 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.
• 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.
• Males must not donate sperm throughout the study drug treatment period.
• Agrees not to participate in another interventional study while on treatment.
• Karnofsky Performance Status 70 or greater is required.

You may not qualify if:

• Prior participation in an APR-246 study.
• Use of umbilical cord blood donor and stem cell source.
• Patient has uncontrolled infection.
• Use of investigational agent within 14 days of pre-HSCT screening or anytime thereafter.
• 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.
• Patient has used experimental therapy for acute GVHD at any time post-transplant.
• Patient requires treatment with supplemental oxygen not including usage of non-invasive CPAP (continuous positive airways pressure) at night.
• Patient has any of the following cardiac abnormalities (as determined by treating physician):
• Myocardial infarct within six months prior to registration
• New York Heart Association Class II or worse heart failure or known LVEF (left ventricular ejection fraction) \< the institution LLN (lower limit normal)
• A history of familial long QT syndrome
• Electrocardiographic evidence of acute ischemia at screening
• Symptomatic atrial or ventricular arrhythmias not controlled by medications
• QTc ≥ 470 ms calculated from a mean of 3 ECG (electrocardiogram) readings using Fridericia's correction (QTcF = QT/RR0.33)
• Bradycardia (\<40 bpm) at screening

Sponsors & Collaborators

• Aprea Therapeutics: lead

Study Sites (7)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21278, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 35816664 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

eprenetapopt; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Senior Medical Advisor
• Organization: Aprea Therapeutics

info@aprea.com

215-948-4119

Study Officials

• Asmita Mishra, MD, PhD

  H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: April 26, 2019
• First Posted: April 30, 2019
• Study Start: September 16, 2019
• Primary Completion: August 27, 2021
• Study Completion: January 14, 2022
• Last Updated: March 17, 2025
• Results First Posted: March 26, 2024

Record last verified: 2025-03

Locations

US (7)