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
- Are there results?
- None posted in the registry
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
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03588078
- Acronym / sponsor ID
- GFM-APR246
- Conditions
- Myelodysplastic Syndrome With Gene Mutation, Acute Myeloid Leukemia With Gene Mutations, Myeloproliferative Neoplasm, Chronic Myelomonocytic Leukemia
- Keywords
- Azacitidine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Collaborators
- Aprea Therapeutics
- Study start
- 15 Sep 2018 (actual)
- Primary completion
- 1 May 2020 (actual)
- Study completion
- 15 May 2021 (actual)
- First posted
- 17 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will receive one dose of protocol therapy
| Arm | Type | Receives |
|---|---|---|
| combination of APR246 and azacitidine | Experimental | Drug: APR-246, Drug: AzacitidineFollowing 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- Age ≥18 years at the time of signing the informed consent form
- 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.
Key exclusion criteria (18 listed)
- 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):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APR-246Also: PRIMA-1MET, Methylated analogue to PRIMA-1Azacitidine at maximum tolerated dose. APR246 at the Dose limited Toxicity (DLT) dose | Drug | combination of APR246 and azacitidine |
| AzacitidineAlso: Mylosar, Vidazaazacitidine is administered subcutaneously (SC) or via IV at 75 mg/m2 | Drug | combination of APR246 and azacitidine |
Primary outcome
Overall Survival
Time frame: 8 months
overall survival at complete remission
1 secondary outcome
Duration of response
Time frame: minimum 24 months it is defined as the time between achieving response and progression of disease
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 33600210Cluzeau 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Fenaux principal investigator
service Hématologie Séniors Hôpital Saint Louis
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03588078, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.