Clinical Trials /

Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine

NCT03588078

Description:

The main purpose of this study is to determine the safe and efficacy of APR-246 in combination with azacitidine as well as to see complete remission of this patients

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Refractory Anemia with Excess Blasts
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine
  • Official Title: A Phase 1b/2 Study to Evaluate the Safety and Efficacy of APR-246 in Combination With Azacitidine for the Treatment of Mutation TP53 (TP53) Mutant Myeloid Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: GFM-APR246
  • NCT ID: NCT03588078

Conditions

  • Myelodysplastic Syndrome With Gene Mutation
  • Acute Myeloid Leukemia With Gene Mutations
  • Myeloproliferative Neoplasm
  • Chronic Myelomonocytic Leukemia

Interventions

DrugSynonymsArms
APR-246PRIMA-1MET, Methylated analogue to PRIMA-1combination of APR246 and azacitidine
AzacitidineMylosar, Vidazacombination of APR246 and azacitidine

Purpose

The main purpose of this study is to determine the safe and efficacy of APR-246 in combination with azacitidine as well as to see complete remission of this patients

Detailed Description

      Patients will be treated for a total of 6 cycles.For patients responding or who have stable
      disease following cycle 6, treatment may continue until one of the following criteria
      applies:

        -  Inter-current illness that prevent further administration of treatment

        -  Unacceptable adverse event(s)

        -  Participant decides to withdraw from the study,

        -  general or specific changes in the participant's condition render the participant
           unacceptable for further treatment in the judgment of the investigator.

        -  Evidence of disease progression by international working Group (IWG) 2006 criteria.

        -  participants who wish not to continue treatment at time of disease assessment at end of
           cycle 6 will complete their end of treatment visit upon completion of cycle 6
    

Trial Arms

NameTypeDescriptionInterventions
combination of APR246 and azacitidineExperimentalFollowing completion of the Dose Finding Phase, we will conduct a dose expansion, whereby patients will be treated with APR-246 administered at the maximum tolerated dose (MTD) with azacitidine on a 28 day cycle utilizing the same dosing as in Phase 1b
  • APR-246
  • Azacitidine

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has signed the Informed Consent (ICF) and is able to comply with protocol
             requirements.

          2. Patient has adequate organ function as defined by the following laboratory values:

               1. Serum creatinine ≤ 2 x upper limit of normal (ULN)

               2. Total serum bilirubin < 1.5 x ULN or total bilirubin ≤ 3.0 x ULN with direct
                  bilirubin within normal range in patients with well documented Gilbert's Syndrome
                  or hemolysis or who required regular blood transfusions

               3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN

          3. Age ≥18 years at the time of signing the informed consent form

          4. Documented diagnosis of myelodysplastic syndrome (MDS), MDS/ myeloproliferative
             neoplasm (MPN), chronic myelomonocytic leukemia (CMML) by World Health organization
             (WHO) criteria or Acute Myeloid Leukemia (AML) with 20-30% myeloblasts (refractory
             anemia with excess blasts in transformation (RAEB-T) by French-American-British (FAB)
             criteria).

          5. Documentation of a TP53 gene mutation by next-generation sequencing (NGS) based on
             central or local evaluation.

          6. Revised International Prognostic Scoring System (IPSS-R) criteria for Intermediate,
             High-risk or Very High-risk.

          7. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 is
             required.

          8. If of childbearing potential, negative pre-treatment urine or serum pregnancy test.

          9. 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:

          1. Patient has a known history of HIV or active hepatitis B or active hepatitis C
             infection (testing not mandatory).

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

               1. symptomatic congestive heart failure

               2. myocardial infarction ≤ 6 months prior to enrollment

               3. unstable angina pectoris

               4. serious uncontrolled cardiac arrhythmia

               5. Corrected QT interval (QTc) ≥ 480 msec

          3. 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.

          4. Prior exposure to azacitidine, decitabine or investigational hypomethylating agent

          5. Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not
             commercially available) for the treatment of MDS, MDS/MPN, CMML or AML within 14 days
             of the first day of study drug treatment.

          6. No concurrent use of erythroid stimulating agents, Granulocyte-colony stimulating
             Factor (G-CSF), Granulocyte Macrophage-colony stimulating factor (GM-CSF) is allowed
             during study except in cases of febrile neutropenia where G-CSF can be used for short
             term. Growth factors must be stopped 14 days prior to study.

          7. Patients with history of allogeneic stem cell transplantation.

          8. Pregnant women are excluded from this study because APR-246 has not been studied in
             pregnant subjects. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:8 months
Safety Issue:
Description:overall survival at complete remission

Secondary Outcome Measures

Measure:Duration of response
Time Frame:minimum 24 months it is defined as the time between achieving response and progression of disease
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Groupe Francophone des Myelodysplasies

Trial Keywords

  • Azacitidine

Last Updated