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Clinical Trial 19825

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03745716

Phase: Phase III
Prinicipal Investigator:

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Study Title

A Phase III Multicenter, Randomized, Open Label Study of APR-246 in Combination with Azacitidine Versus Azacitidine Alone for the Treatment of TP53 Mutant Myelodysplastic Syndromes


A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone. *This study is being conducted at both Moffitt Cancer Center and at Memorial Healthcare, Hollywood Florida


Primary Objective: 1. To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR), and duration of CR with APR-246 + azacitidine treatment vs. azacitidine only. Secondary Objectives: To measure the following with APR-246 + azacitidine treatment vs. azacitidine alone: 1. Overall response rate (ORR): CR, PR, mCR, mCR+HI, HI 2. Duration of Response (DOR) 3. Rate and time to acute myeloid leukemia (AML) transformation 4. Overall survival (OS) 5. Progression free survival (PFS) 6. Transition rate to hematopoietic stem cell transplant (HSCT) 7. Safety profile 8. Rate of red blood cell (RBC) and/or platelet transfusion independence (TI) for 56 days (8 weeks) 9. Pharmacokinetics of APR-246 and influence of APR-246 on azacitidine pharmacokinetics




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

Inclusion Criteria

  • Signed Informed Consent (ICF) and is able to comply with protocol requirements
  • Documented diagnosis of MDS, according to World Health Organization (WHO) classification
  • Adequate organ function
  • Age ≥18 years at the time of signing the informed consent form (ICF)
  • Having at least one TP53 mutation which is not benign or likely benign
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • If of childbearing potential, negative pre-treatment urine or serum pregnancy test
  • If of childbearing potential (males and females), willing to use an effective form of contraception such as latex condom, hormonal birth control, intrauterine device or double barrier method during chemotherapy treatment and for at least six months thereafter

  • Exclusion Criteria

    Exclusion Criteria:

  • Known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
  • Any of the cardiac abnormalities listed in protocol (as determined by treating MD)
  • Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
  • Prior exposure to azacitidine, decitabine or investigational hypomethylating agent or induction chemotherapy for MDS or AML. Note: Intensive chemotherapy for any other prior cancer is not exclusionary.
  • Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment
  • Concurrent use of erythroid stimulating agents, G-CSF or GM-CSF within 14 days of the first day of study drug treatment.
  • History of allogeneic stem cell transplantation
  • Pregnant women are excluded from this study because APR-246 has not been studied in pregnant patients. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with APR 246, breastfeeding should be discontinued if the mother is treated with APR-246.
  • Active uncontrolled infections

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