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Clinical Trial 20036

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03931291

Phase: Phase II
Prinicipal Investigator:

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Study 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


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.


Primary: 1. To assess relapse-free survival (RFS) in patients with TP53 mutated AML or MDS who receive combination maintenance treatment with APR-246 with azacitidine after undergoing allogeneic hematopoietic stem cell transplant (HSCT). 2. To evaluate the safety and tolerability of APR-246 in combination with azacitidine as maintenance treatment post-HSCT. Secondary: 1. To assess the overall survival (OS). 2.To asses non-relapse mortality (NRM). 3.To assess time to progression (TTP). 4.To evaluate cumulative incidence of Grades II-IV and III-IV acute graft versus host disease (GVHD). 5.To evaluate 12-month cumulative incidence of mild, moderate, and severe GVHD. 6.To evaluate post-transplant engraftment via chimerism studies in blood.




APR-246 (); azacitidine (5-azacitidine)

Inclusion Criteria

  • Participant must have previously met pre-transplantation eligibility.
  • Participant has received one allogeneic transplant for AML or MDS. At time of treatment, participant must in morphologic remission for AML or MDS as defined as >Any standard (non-study) conditioning [MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)] will be permitted.
  • Participant is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
  • Participant is in complete remission after the transplant and has achieved engraftment. .
  • Participants 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.
  • Participant has adequate organ function as defined by the protocol.

  • Exclusion Criteria

  • Prior participation in an APR-246 study.
  • Use of umbilical cord blood donor and stem cell source.
  • Participant 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.
  • Participant has used experimental therapy for acute GVHD at any time post-transplant.
  • Participant requires treatment with supplemental oxygen not including usage of non-invasive CPAP (continuous positive airways pressure) at night.
  • Participant 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 III or IV heart failure or known LVEF (left ventricular ejection fraction) >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. Participants with QTc ≥ 470 ms and bundle branch block and/or pacemaker rhythm may be enrolled after approval by Medical Monitor.

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