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History of Changes for Study: NCT03588078
Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine
Latest version (submitted January 29, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 3, 2018 None (earliest Version on record)
2 November 13, 2018 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 February 5, 2019 Contacts/Locations, Eligibility, Study Design and Study Status
4 March 26, 2019 IPDSharing, Contacts/Locations and Study Status
5 August 6, 2019 Study Status, Contacts/Locations and Eligibility
6 August 9, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
7 October 25, 2019 Study Status
8 January 29, 2020 Recruitment Status and Study Status
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Study NCT03588078
Submitted Date:  July 3, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: GFM-APR246
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
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2018
Overall Status: Not yet recruiting
Study Start: September 15, 2018
Primary Completion: May 1, 2020 [Anticipated]
Study Completion: May 15, 2021 [Anticipated]
First Submitted: June 20, 2018
First Submitted that
Met QC Criteria:
July 3, 2018
First Posted: July 17, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
July 3, 2018
Last Update Posted: July 17, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Groupe Francophone des Myelodysplasies
Responsible Party: Sponsor
Collaborators: Aprea Therapeutics
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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
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
Open or close this module Conditions
Conditions: Myelodysplastic Syndrome With Gene Mutation
Acute Myeloid Leukemia With Gene Mutations
Myeloproliferative Neoplasm
Chronic Myelomonocytic Leukemia
Keywords: Azacitidine
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Single Group Assignment
Participants will receive one dose of protocol therapy
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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:
  • PRIMA-1MET
  • Methylated analogue to PRIMA-1
Drug: Azacitidine
azacitidine is administered subcutaneously (SC) or via IV at 75 mg/m2
Other Names:
  • Mylosar
  • Vidaza
Open or close this module Outcome Measures
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 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: Fatiha Chermat
Telephone: +330171207059
Email: fatiha.chermat-ext@aphp.fr
Central Contact Backup: Thomas Cluzeau, MD
Telephone: +33492035841
Email: cluzeau.t@chu-nice.fr
Study Officials: Pierre Fenaux
Principal Investigator
service Hématologie Séniors Hôpital Saint Louis
Locations: France
Hôpital Archet 1
Nice, France, 06200
Contact:Contact: Thomas CLUZEAU, Prof 33492035844 cluzeau.t@chu-nice.fr
Contact:Principal Investigator: Pierre Fenaux, Pr
Hôpital Saint Louis - Hématologie Séniors
Paris, France, 75010
Contact:Contact: Pierre Fenaux, MD 033170207022 pierre.fenaux@sls.aphp.fr
Contact:Principal Investigator: Pierre Fenaux, MD
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Links:
Available IPD/Information:

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