Acute Myeloid LeukaemiaPhase 1/2NCT04629443
Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia
A Phase 1/2 study testing S 64315 (also referred as MIK665) and azacitidine in people with Acute Myeloid Leukaemia, run by Institut de Recherches Internationales Servier at 7 sites in 4 countries.
Trial summary
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 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 Leukaemia
- What is being tested?
- S 64315 (also referred as MIK665) and azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 17 Feb 2021to 25 Aug 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients aged ≥ 18 years
- Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization 2016 classification (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3 classification) with: relapsed or refractory disease and without established alternative therapy, or secondary to MyeloDysplastic Syndrome and without established alternative therapy or, newly diagnosed AML, not previously treated for AML and who are not candidate for intensive chemotherapy due to age or comorbidities.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.
Who cannot join
- Previous myeloproliferative syndrome (MPS).
- Patients previously treated with any Mcl-1 inhibitor.
- Patients who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 5.0, prior to the first IMP administration.
- Severe or uncontrolled active acute or chronic infection.
- Uncontrolled hepatitis B or C infection.
- Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
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- Troponin > ULN (Upper Limit of reference range) or Troponin T > ULN if Troponin I cannot be assessed.
- Clinically significant cardiac dysfunction (including New York Heart Association class ≥II heart failure, Left Ventricular Ejection Fraction (LVEF) < 50% as assessed by echocardiography (ECHO) or Multi-Gated Acquisition (MUGA) scan).
- QT prolongation defined as QTc (QT interval corrected for heart rate) interval (corrected with Fridericia's formula) > 450 ms for males and > 470 ms for females, obtained from triplicate 12-lead ECG.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
- Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Australia2 sites
Victorian Comprehensive Cancer Centre
Melbourne, 3002
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
Melbourne, 3004
France2 sites
Institut Paoli-Calmettes
Marseille
Hôpital Saint Antoine
Paris, 75012
Spain2 sites
H. Universitario Valle de Hebrón Servicio de Hematología
Barcelona, 08035
H. Universitario La Fe Servicio de Hematologia
Valencia, 46026
United States1 site
University of Texas MD Anderson Cancer Center Department of Leukemia, Division of Cancer Medicine
Houston, Texas, 77030
About this study
Official title: Phase I/II, International, Multicentre, Open-label, Non-randomised, Non-comparative, Study Evaluating the Safety, Tolerability and Clinical Activity of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukaemia (AML)
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.
- Conditions
- Acute Myeloid Leukaemia
- Being tested
- S 64315 (also referred as MIK665) and azacitidine
- Keywords
- Acute Myeloid Leukaemia, Oncology, Mcl-1 inhibitor, Azacitidine, Combination, Phase I/II, International, Safety, Maximum tolerated dose
- 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.
S 64315 (also referred as MIK665) and azacitidineDrug
The combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) administered via intravenous (IV) infusion over at least 2 hours.
During the combination treatment period S64315 will be administered according to a dose escalation scheme starting at 50 mg up to 250 mg might be explored. The schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen of azacitidine administered at 75 mg/m² via subcutaneous (SC) injection for 7 days from D1 to D7 of each cycle followed by a rest period of 21 days.
| Study group | Role | What they receive |
|---|---|---|
| S64315 (also referred as MIK665) with azacitidine | Experimental | Not described Receives: Drug: S 64315 (also referred as MIK665) 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 - Dose Escalation)
Incidence of DLTs starting from the Lead-In Dose period to the end of the first cycle of treatment of S64315 in combination with azacitidine.
Measured: Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
Incidence and severity of AEs according to NCI CTCAE v5.0
Measured: an average of 6 months
Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)
Incidence and severity of SAEs according to NCI CTCAE v5.0
Measured: Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)
Number of Participants With Dose Interruptions (Phase I - Dose Escalation)
Measured: Through study completion, an average of 6 months
Number of Participants With Dose Reductions (Phase I - Dose Escalation)
Measured: Through study completion, an average of 6 months
Dose Intensity for S64315 (Phase I - Dose Escalation)
Measured: Through study completion, an average of 6 months
Dose Intensity for Azacitidine (Phase I - Dose Escalation)
Measured: Through study completion, an average of 6 months
Secondary outcomes (7)
Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)
Overall survival (OS)
Measured: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Duration of response (DOR)
Measured: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Best overall response (BOR)
Measured: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Progression-free survival (PFS)
Measured: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Disease-free survival (DFS)
Measured: Through study completion, an average of 6 months
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)
Measured: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)
Measured: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start17 Feb 2021
- Primary completion25 Aug 2023
- Study completion25 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukaemiaStudies 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
- 17 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
- NCT04629443
- Sponsor's protocol ID
- CL1-64315-004
- Other IDs
- 2019-004896-38, 2019
- Status last verified
- May 2024
- First submitted
- 3 Nov 2020
- Last updated
- 6 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II, International, Multicentre, Open-label, Non-randomised, Non-comparative, Study Evaluating the Safety, Tolerability and Clinical Activity of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukaemia (AML)
- ClinicalTrials.gov ID
- NCT04629443
- Acronym / sponsor ID
- CL1-64315-004
- Conditions
- Acute Myeloid Leukaemia
- Keywords
- Acute Myeloid Leukaemia, Oncology, Mcl-1 inhibitor, Azacitidine, Combination, Phase I/II, International, Safety
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Study start
- 17 Feb 2021 (actual)
- Primary completion
- 25 Aug 2023 (actual)
- Study completion
- 25 Aug 2023 (actual)
- First posted
- 16 Nov 2020 (actual)
- Results
- Posted 6 Jun 2024
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 S64315 with azacitidine in patients with acute myeloid leukaemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| S64315 (also referred as MIK665) with azacitidine | Experimental | Drug: S 64315 (also referred as MIK665) and azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged ≥ 18 years
- Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization 2016 classification (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3 classification) with: relapsed or refractory disease and without established alternative therapy, or secondary to MyeloDysplastic Syndrome and without established alternative therapy or, newly diagnosed AML, not previously treated for AML and who are not candidate for intensive chemotherapy due to age or comorbidities.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.
Key exclusion criteria (11 listed)
- Previous myeloproliferative syndrome (MPS).
- Patients previously treated with any Mcl-1 inhibitor.
- Patients who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 5.0, prior to the first IMP administration.
- Severe or uncontrolled active acute or chronic infection.
- Uncontrolled hepatitis B or C infection.
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 |
|---|---|---|
| S 64315 (also referred as MIK665) and azacitidineThe combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) administered via intravenous (IV) infusion over at least 2 hours. During the combination treatment period S64315 will be administered according to a dose escalation scheme starting at 50 mg up to 250 mg might be explored. The schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen of azacitidine administered at 75 mg/m² via subcutaneous (SC) injection for 7 days from D1 to D7 of each cycle followed by a rest period of 21 days. | Drug | S64315 (also referred as MIK665) with azacitidine |
Primary outcome
Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)
Time frame: Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
Incidence of DLTs starting from the Lead-In Dose period to the end of the first cycle of treatment of S64315 in combination with azacitidine.
Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
Time frame: an average of 6 months
Incidence and severity of AEs according to NCI CTCAE v5.0
Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)
Time frame: Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)
Incidence and severity of SAEs according to NCI CTCAE v5.0
Number of Participants With Dose Interruptions (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Number of Participants With Dose Reductions (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Dose Intensity for S64315 (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Dose Intensity for Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
7 secondary outcomes
Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Time frame: Through study completion, an average of 6 months
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)
Time frame: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)
Time frame: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing S 64315 (also referred as MIK665) and azacitidine in people with Acute Myeloid Leukaemia, run by Institut de Recherches Internationales Servier at 7 sites in 4 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 4 inclusion and 11 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 6 Jun 2024. 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 Australia, France, Spain, United States. 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?
Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 - Dose Escalation) (time frame: Day -13 to Cycle 1 Day 28 (each cycle is 28 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jun 2024.