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Trial record 1 of 1 for:    NCT03588078
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Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine

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ClinicalTrials.gov Identifier: NCT03588078
Recruitment Status : Unknown
Verified January 2020 by Groupe Francophone des Myelodysplasies.
Recruitment status was:  Active, not recruiting
First Posted : July 17, 2018
Last Update Posted : January 30, 2020
Aprea Therapeutics
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome With Gene Mutation Acute Myeloid Leukemia With Gene Mutations Myeloproliferative Neoplasm Chronic Myelomonocytic Leukemia Drug: APR-246 Drug: Azacitidine Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Participants will receive one dose of protocol therapy
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 15, 2018
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 15, 2021

Arm Intervention/treatment
Experimental: combination of APR246 and azacitidine
Following 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
Drug: APR-246
Azacitidine at maximum tolerated dose. APR246 at the Dose limited Toxicity (DLT) dose
Other Names:
  • Methylated analogue to PRIMA-1

Drug: Azacitidine
azacitidine is administered subcutaneously (SC) or via IV at 75 mg/m2
Other Names:
  • Mylosar
  • Vidaza

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 8 months ]
    overall survival at complete remission

Secondary Outcome Measures :
  1. Duration of response [ Time Frame: minimum 24 months it is defined as the time between achieving response and progression of disease ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 non-proliferative AML (ie with WBC < 20 G/l)
  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. QTc ≥ 470 msec (≥ 500 msec in the presence of RBBB) calculated from a mean of 3 ECG readings using Fridericia's correction (QTcF = QT/RR0.33)
    6. bradycardia (<40 bpm)
    7. known left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by ECHO
    8. clinically significant pericardial disease
    9. electrocardiographic evidence of acute ischemia
    10. familial history of long QT syndrome
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03588078

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Bruno Quesnel
Lille, France, 59037
Dr Pierre Peterlin and Pr Patrice Chevalier
Nantes, France, 44093
Hôpital Archet 1
Nice, France, 06200
Hôpital Saint Louis - Hématologie Séniors
Paris, France, 75010
Hôpital Cochin/Service d'Hématologie
Paris, France, 75679
Aspasia Stamatoullas
Rouen, France, 76038
Odile Beyne Rosy
Toulouse, France, 31059
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Aprea Therapeutics
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Principal Investigator: Pierre Fenaux service Hématologie Séniors Hôpital Saint Louis
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT03588078    
Other Study ID Numbers: GFM-APR246
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Groupe Francophone des Myelodysplasies:
Additional relevant MeSH terms:
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Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors