Myelodysplastic Syndrome With Gene MutationPhase 1/2NCT03588078
Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine
A Phase 1/2 study testing APR-246 and Azacitidine in people with Myelodysplastic Syndrome With Gene Mutation and Acute Myeloid Leukemia With Gene Mutations, run by Groupe Francophone des Myelodysplasies at 7 sites in France.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome With Gene Mutation, Acute Myeloid Leukemia With Gene Mutations, Myeloproliferative Neoplasm
- What is being tested?
- APR-246 and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 7 sitesFrance
- Study dates
- 15 Sep 2018to 15 May 2021
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
- Patient has adequate organ function as defined by the following laboratory values:
- Serum creatinine ≤ 2 x upper limit of normal (ULN)
- 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
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
- Age ≥18 years at the time of signing the informed consent form
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- 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)
- Documentation of a TP53 gene mutation by next-generation sequencing (NGS) based on central or local evaluation.
- Revised International Prognostic Scoring System (IPSS-R) criteria for Intermediate, High-risk or Very High-risk.
- An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 is required.
- 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.
Who cannot join
- Patient has a known history of HIV or active hepatitis B or active hepatitis C infection (testing not mandatory).
- Patient has any of the following cardiac abnormalities (as determined by treating MD):
- symptomatic congestive heart failure
- myocardial infarction ≤ 6 months prior to enrollment
- unstable angina pectoris
- serious uncontrolled cardiac arrhythmia
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- 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)
- bradycardia (<40 bpm)
- known left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by ECHO
- clinically significant pericardial disease
- electrocardiographic evidence of acute ischemia
- familial history of long QT syndrome
- 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
- 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.
- 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.
- Patients with history of allogeneic stem cell transplantation.
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
Bruno Quesnel
Lille, 59037
Dr Pierre Peterlin and Pr Patrice Chevalier
Nantes, 44093
Hôpital Archet 1
Nice, 06200
Hôpital Saint Louis - Hématologie Séniors
Paris, 75010
Hôpital Cochin/Service d'Hématologie
Paris, 75679
Aspasia Stamatoullas
Rouen, 76038
Odile Beyne Rosy
Toulouse, 31059
About this study
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
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
Read the 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
- Conditions
- Myelodysplastic Syndrome With Gene Mutation, Acute Myeloid Leukemia With Gene Mutations, Myeloproliferative Neoplasm, Chronic Myelomonocytic Leukemia
- Being tested
- APR-246, Azacitidine
- Keywords
- Azacitidine
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APR-246Drug
Also called PRIMA-1MET, Methylated analogue to PRIMA-1
Azacitidine at maximum tolerated dose. APR246 at the Dose limited Toxicity (DLT) dose
AzacitidineDrug
Also called Mylosar, Vidaza
azacitidine is administered subcutaneously (SC) or via IV at 75 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| combination of APR246 and azacitidine | Experimental | 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 Receives: Drug: APR-246; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
overall survival at complete remission
Measured: 8 months
Secondary outcomes (1)
Duration of response
Measured: minimum 24 months it is defined as the time between achieving response and progression of disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start15 Sep 2018
- Primary completion1 May 2020
- Study completion15 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic Syndrome With Gene MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will receive one dose of protocol therapy
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Aprea Therapeutics
- Responsible party
- Sponsor
- Investigators
- Pierre Fenaux, Principal investigator, service Hématologie Séniors Hôpital Saint Louis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588078
- Sponsor's protocol ID
- GFM-APR246
- Status last verified
- Sep 2026
- First submitted
- 20 Jun 2018
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cluzeau T, Sebert M, Rahme R, Cuzzubbo S, Lehmann-Che J, Madelaine I, Peterlin P, Beve B, Attalah H, Chermat F, Miekoutima E, Rauzy OB, Recher C, Stamatoullas A, Willems L, Raffoux E, Berthon C, Quesnel B, Loschi M, Carpentier AF, Sallman DA, Komrokji R, Walter-Petrich A, Chevret S, Ades L, Fenaux P. Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myelodysplasies (GFM). J Clin Oncol. 2021 May 10;39(14):1575-1583. doi: 10.1200/JCO.20.02342. Epub 2021 Feb 18.
PubMed 33600210