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

Sponsor
Aprea Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03931291
Collaborator
(none)
33
7
1
28
4.7
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of APR-246 in Combination With Azacitidine as Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplant
Actual Study Start Date :
Sep 16, 2019
Actual Primary Completion Date :
Aug 27, 2021
Actual Study Completion Date :
Jan 14, 2022

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. To assess relapse-free survival (RFS) in patients with TP53 mutated AML or MDS after undergoing allogeneic hematopoietic stem cell transplant (HSCT). [Through study completion, an average of 1 year]

      Relapse-free survival (RFS) at 12 months 2. To evaluate the safety and tolerability of APR-246 in combination with azacitidine as maintenance treatment post-HSCT.

    Eligibility Criteria

    Criteria

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

    1. 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.

    2. 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.

    3. Males must not donate sperm throughout the study drug treatment period.

    4. Agrees not to participate in another interventional study while on treatment.

    5. 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):

    9. Myocardial infarct within six months prior to registration

    10. New York Heart Association Class II or worse heart failure or known LVEF (left ventricular ejection fraction) < the institution LLN (lower limit normal)

    11. A history of familial long QT syndrome

    12. Electrocardiographic evidence of acute ischemia at screening

    13. Symptomatic atrial or ventricular arrhythmias not controlled by medications

    14. QTc ≥ 470 ms calculated from a mean of 3 ECG (electrocardiogram) readings using Fridericia's correction (QTcF = QT/RR0.33)

    15. Bradycardia (<40 bpm) at screening

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612
    2 Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21278
    3 Massachusetts General Hospital Boston Massachusetts United States 02114
    4 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    5 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    6 Vanderbilt Ingram Cancer Center Nashville Tennessee United States 37232
    7 Fred Hutchinson Cancer Center Seattle Washington United States 98109

    Sponsors and Collaborators

    • Aprea Therapeutics

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Aprea Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03931291
    Other Study ID Numbers:
    • A19-11172
    First Posted:
    Apr 30, 2019
    Last Update Posted:
    Jan 19, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 19, 2022