Acute Myeloid LeukemiaPhase 1/2NCT04742101
Phase I/II Trial of S65487 Plus Azacitidine in Acute Myeloid Leukemia
A Phase 1/2 study testing S65487 and azacitidine in people with Acute Myeloid Leukemia, run by Institut de Recherches Internationales Servier at 11 sites in 6 countries.
Trial summary
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S65487 with azacitidine in patients with acute myeloid leukaemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- S65487 and azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 10 Mar 2021to 27 Mar 2026
- 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
- Male or female participant aged ≥ 18 years old
- Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes:
- Previous myelodysplastic syndrome transformed
- AML due to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 3 years
- Participants not eligible for standard induction chemotherapy
- Aged ≥ 75 years old
Show all 17Show fewer
- Or Age ≥18 years with at least one of the following comorbidities:
- Clinically significant heart or lung comorbidities, as reflected by at least one of:
- Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
- Forced expiratory volume in 1 second (FEV1) ≤65% of expected
- Other contraindication(s) to anthracycline therapy (must be documented)
- Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented
- ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG ≤ 2.
- Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol.
- Adequate renal and hepatic function
- Circulating White Blood Cell Count (WBC count) < 25*109 G/L (with or without use of hydroxycarbamide/leukapheresis)
- Serum potassium, serum calcium, serum phosphates, serum magnesium within normal limits with or without supplementation.
Who cannot join
- Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery
- Any radiotherapy within 3 weeks before the first IMP administration,
- Allogenic stem cell transplant within 3 months before the first IMP administration and/or participants with active Graft-versus-host disease within 3 months before the first IMP administration and/or participants who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or participant who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration
- Acute promyelocytic leukemia (APL, French-American-British M3 classification)
- Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 3, 2019 for Acute Myeloid Leukemia
- Treatment with hypomethylating agents (decitabine/azacitidine) or Venetoclax for AHD (antecedent hematologic disorders) in the 3 months prior to the first IMP intake
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
Spain3 sites
Hospital 12 de Octubre Servicio de Hematología
Madrid, 28041
C. Universidad de Navarra Servicio de Hematologia
Pamplona, 31008
H. Universitario La Fe Servicio de Hematologia
Valencia, 46026
United Kingdom3 sites
Western General Hospital
Edinburgh, EH4 2XU
University College London - Hospitals NHS Foundation Trust
London, NW1 2PG
The Christie NHS foundation Trust
Manchester, M20 4BX
South Korea2 sites
Seoul National University Hospital - Department of Hematology-Oncology
Seoul, 03080
Samsung Medical Center - Division of Hematology-Oncology
Seoul, 06351
Hungary1 site
Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika Klinikai Farmakológiai Részleg
Budapest, H-1083
Poland1 site
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie Klinika Transplantacji Szpiku i Onkohematologii pokoj 4.041 ul. Wybrzeze Armii Krajowej 15
Gliwice, 44-102
About this study
Official title: Phase I / II, Open Label, Dose Escalation Part (Phase I) Followed by Non-comparative Expansion Part (Phase II), Multi-centre Study, Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a Bcl2 Inhibitor Combined With Azacitidine in Adult Patients With Previously Untreated Acute Myeloid Leukemia Not Eligible for Intensive Treatment
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S65487 with azacitidine in patients with acute myeloid leukaemia.
Read the detailed description
The study is designed in two parts: A dose escalation phase I part, and a dose expansion phase II part with an additional potential expansion cohort.
During dose escalation of S65487 in combination with azacitidine, only S65487 agent dose will escalate and a DDI (Drug-Drug interaction) assessment between S65487 and posaconazole (antifungal drug) will be performed. A ramp-up dose of S65487 will be administered on the first two days of cycle 1, then the full dose of S65487 will be administered for the remainder of cycle 1. Each treatment cycle is 28 days.
For the expansion phase, the dose will be the RP2D (Recommended Phase 2 Dose) determined during phase I part. An additional potential expansion cohort will be included if there is more than one promising dose/schedule candidate.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- S65487 and azacitidine
- Keywords
- Acute Myeloid Leukemia, Dose escalation, Phase I/II, Azacitidine, Combination, Oncology
- Medical subject headings
- Leukemia, Myeloid, Acute, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S65487 and azacitidineDrug
Treatment cycle of combination of S65487 and azacitidine during 4 weeks. Two administration schedules are set up. S65487 will be administered via intravenous (IV) infusion. Azacitidine will be administered via either subcutaneous (SC) or Intravenous (IV) infusion according to local practices.
| Study group | Role | What they receive |
|---|---|---|
| S65487 with azacitidine | Experimental | Not described Receives: Drug: S65487 and azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT) (phase I part)
DLT assessment at the end of cycle 1
Measured: Through the end of first cycle (each cycle is 28 days)
Adverse Event (phase I part)
AE recording throughout the study evaluated according to CTCAE v5.0, dose interruptions, reductions, and intensity
Measured: Through study completion, an average of 3 years ans 5 months
Complete Remission (CR) rate (phase II part)
CR rate is defined as the proportion of subjects who achieve complete response. Response is evaluated based on the "'Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel" (Döhner, 2022).
Measured: Through study completion, up to 3 years and 5 months
Secondary outcomes (4)
PharmacoKinetics - maximum Concentration at the End of the infusion (Cinf) (phase I and phase II parts)
PK parameters of S65487, azacitidine and potential metabolite(s)
Measured: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 (schedule 1, first two cohorts), Cycle 2 Day 8 (from Cohort 3), or Day 15 (first two cohorts)(each cycle is 28 days)
PharmacoKinetics - Area Under the Curve (AUC) (phase I and phase II parts)
PK parameters of S65487, azacitidine and potential metabolite(s)
Measured: Cycle 1 Day 8 to Day 9, Cycle 2 Day 8 to Day 9 (from cohort 3), or Day 15 to Day 16 (first two cohorts)(each cycle is 28 days)
Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)
Complete Remission rate
Measured: Through study completion, an average of 3 years and 5 months
Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)
Progression Free Survival
Measured: Through study completion, an average of 3 years and 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2021
- Study start10 Mar 2021
- Primary completion27 Mar 2026
- Study completion27 Mar 2026
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 Acute Myeloid LeukemiaStudies 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
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04742101
- Sponsor's protocol ID
- CL1-65487-003
- Other IDs
- 2020-003061-19
- Status last verified
- May 2026
- First submitted
- 14 Dec 2020
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Publications
Pierola AA, De Botton S, Jan JH, Campbell V, O'Nions J, Calbacho M, Ervin-Hayes AL, Keagle K, Maillard A, Beneton M, Romagnoli M, Broniscer A. Trial in Progress: An Open Label Phase I/II, Multicenter Study Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a BCL-2 Inhibitor Combined with Azacitidine in Adults with Previously Untreated Acute Myeloid Leukemia Ineligible for Intensive Treatment. Blood. 2023 Nov 2;142(Supplement 1):1555. doi: https://doi.org/10.1182/blood-2023-180795
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I / II, Open Label, Dose Escalation Part (Phase I) Followed by Non-comparative Expansion Part (Phase II), Multi-centre Study, Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a Bcl2 Inhibitor Combined With Azacitidine in Adult Patients With Previously Untreated Acute Myeloid Leukemia Not Eligible for Intensive Treatment
- ClinicalTrials.gov ID
- NCT04742101
- Acronym / sponsor ID
- CL1-65487-003
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, Dose escalation, Phase I/II, Azacitidine, Combination, Oncology
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Study start
- 10 Mar 2021 (actual)
- Primary completion
- 27 Mar 2026 (actual)
- Study completion
- 27 Mar 2026 (actual)
- First posted
- 5 Feb 2021 (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 purpose of this study is to assess the safety, tolerability and clinical activity of the combination S65487 with azacitidine in patients with acute myeloid leukaemia.
Detailed description
The study is designed in two parts: A dose escalation phase I part, and a dose expansion phase II part with an additional potential expansion cohort.
During dose escalation of S65487 in combination with azacitidine, only S65487 agent dose will escalate and a DDI (Drug-Drug interaction) assessment between S65487 and posaconazole (antifungal drug) will be performed. A ramp-up dose of S65487 will be administered on the first two days of cycle 1, then the full dose of S65487 will be administered for the remainder of cycle 1. Each treatment cycle is 28 days.
For the expansion phase, the dose will be the RP2D (Recommended Phase 2 Dose) determined during phase I part. An additional potential expansion cohort will be included if there is more than one promising dose/schedule candidate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| S65487 with azacitidine | Experimental | Drug: S65487 and azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female participant aged ≥ 18 years old
- Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes:
- Participants not eligible for standard induction chemotherapy
- ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG ≤ 2.
- Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol.
Key exclusion criteria (6 listed)
- Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery
- Any radiotherapy within 3 weeks before the first IMP administration,
- Allogenic stem cell transplant within 3 months before the first IMP administration and/or participants with active Graft-versus-host disease within 3 months before the first IMP administration and/or participants who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or participant who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration
- Acute promyelocytic leukemia (APL, French-American-British M3 classification)
- Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 3, 2019 for Acute Myeloid Leukemia
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 |
|---|---|---|
| S65487 and azacitidineTreatment cycle of combination of S65487 and azacitidine during 4 weeks. Two administration schedules are set up. S65487 will be administered via intravenous (IV) infusion. Azacitidine will be administered via either subcutaneous (SC) or Intravenous (IV) infusion according to local practices. | Drug | S65487 with azacitidine |
Primary outcome
Dose Limiting Toxicity (DLT) (phase I part)
Time frame: Through the end of first cycle (each cycle is 28 days)
DLT assessment at the end of cycle 1
Adverse Event (phase I part)
Time frame: Through study completion, an average of 3 years ans 5 months
AE recording throughout the study evaluated according to CTCAE v5.0, dose interruptions, reductions, and intensity
Complete Remission (CR) rate (phase II part)
Time frame: Through study completion, up to 3 years and 5 months
CR rate is defined as the proportion of subjects who achieve complete response. Response is evaluated based on the "'Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel" (Döhner, 2022).
4 secondary outcomes
PharmacoKinetics - maximum Concentration at the End of the infusion (Cinf) (phase I and phase II parts)
Time frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 (schedule 1, first two cohorts), Cycle 2 Day 8 (from Cohort 3), or Day 15 (first two cohorts)(each cycle is 28 days)
PharmacoKinetics - Area Under the Curve (AUC) (phase I and phase II parts)
Time frame: Cycle 1 Day 8 to Day 9, Cycle 2 Day 8 to Day 9 (from cohort 3), or Day 15 to Day 16 (first two cohorts)(each cycle is 28 days)
Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)
Time frame: Through study completion, an average of 3 years and 5 months
Assessment of anti-leukemic activity of S65487 combined to azacitidine (phase I and phase II parts)
Time frame: Through study completion, an average of 3 years and 5 months
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 18 May 2026.
- BackgroundPierola AA, De Botton S, Jan JH, Campbell V, O'Nions J, Calbacho M, Ervin-Hayes AL, Keagle K, Maillard A, Beneton M, Romagnoli M, Broniscer A. Trial in Progress: An Open Label Phase I/II, Multicenter Study Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a BCL-2 Inhibitor Combined with Azacitidine in Adults with Previously Untreated Acute Myeloid Leukemia Ineligible for Intensive Treatment. Blood. 2023 Nov 2;142(Supplement 1):1555. doi: https://doi.org/10.1182/blood-2023-180795
- Find Results on Servier Clinical Trial Data websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
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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.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing S65487 and azacitidine in people with Acute Myeloid Leukemia, run by Institut de Recherches Internationales Servier at 11 sites in 6 countries.
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 17 inclusion and 6 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 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Spain, United Kingdom, South Korea, France, Hungary and 1 more country. 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?
Dose Limiting Toxicity (DLT) (phase I part) (time frame: Through the end of first cycle (each cycle is 28 days)). The study lists 3 primary outcomes in all. 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 NCT04742101, 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 18 May 2026.