Acute Myeloid Leukaemia (AML)Phase 1NCT02979366
Phase I Study of S64315 Administred Intravenously in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome
A Phase 1 study testing S64315 once a week and S64315 twice a week in people with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS), run by Institut de Recherches Internationales Servier at 9 sites in 4 countries.
Trial summary
The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS)
- What is being tested?
- S64315 once a week and S64315 twice a week
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 15 Mar 2017to 11 May 2020
- Phase
- Phase 1
- 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 aged ≥ 18 years;
- Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):
- with relapsed or refractory disease without established alternative therapy or
- secondary to MDS treated at least by hypomethylating agent or
- > 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative chemotherapy Or Patients with cytologically confirmed and documented MDS), in relapse or refractory after previous treatment line including at least one hypomethylating agent and have ≥10% bone marrow blasts;
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
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- Circulating white blood cells < 10^9 /L (with or without use of hydroxycarbamide).
- Adequate renal function defined as:
- Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2.
- LDH < 2 x ULN
- Adequate hepatic function defined as:
- AST and ALT ≤ 1.5 x ULN
- Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome (confirmed by the UGT1A1 polymorphism analysis), who are excluded if total bilirubin>3.0 x ULN or direct bilirubin > 1.5 x ULN
- Serum CK/CPK ≤2.5 x ULN.
Who cannot join
- Unlikely to cooperate in the study.
- Participant already enrolled in the study who has received at least one S64315 infusion.
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- Participation in another interventional study requiring investigational treatment intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first dose of S64315 (participation in non-interventional registries or epidemiological studies is allowed).
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03)
- Unresolved ≥ CTCAE grade 2 diarrhoea or medical conditions associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease)
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- Known carriers of HIV antibodies
- Known history of significant liver disease
- Uncontrolled hepatitis B or C infection
- Known active or chronic pancreatitis
- History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
France3 sites
Institut Paoli-Calmettes Departement d'Hématologie
Marseille, 13009
Hôpital Saint-Antoine Département d'Hematologie Clinique et de Thérapie cellulaire
Paris, 75012
Institut Universitaire du Cancer Toulouse Oncopole
Toulouse, 31059 Cedex9
United States2 sites
The University of Texas MD Anderson Cancer Center, Department of Leukemia, Division of Cancer Medicine
Houston, Texas, 77030
Patient Care Location: Smilow Cancer Hospital at Yale
New Haven, Connecticut, 06511
Australia2 sites
The Alfred Hospital Department of Haematology
Melbourne, 3004
Royal Melbourne Hospital, Department of Clinical Haematology and BMT Service
Melbourne, 3050
Spain2 sites
Hospital Universitario Vall d' Hebron/VHIO Hematology Department
Barcelona, 08035
Hospital Universitario La Fe Hematology Department
Valencia, 46026
About this study
Official title: Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)
The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.
- Being tested
- S64315 once a week, S64315 twice a week
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S64315 once a weekDrug
Also called MIK665
S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours once every week (21- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed.
S64315 twice a weekDrug
Also called MIK665
S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours twice every week (28- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed.
| Study group | Role | What they receive |
|---|---|---|
| S64315 (also referred as MIK665) administered once a week | Experimental | Not described Receives: Drug: S64315 once a week |
| S64315 (also referred as MIK665) administered twice a week | Experimental | Not described Receives: Drug: S64315 twice a week |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs during the first cycle of treatment with single agent S64315
Measured: 21-day cycle 1
Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs
Measured: From first dose until 30 days after the last dose administration
Tolerability: Dose interruptions
Measured: From first dose until 30 days after the last dose administration
Tolerability: Dose reductions
Measured: From first dose until 30 days after the last dose administration
Tolerability: Dose intensity
Measured: From first dose until 30 days after the last dose administration
Secondary outcomes (13)
Concentration at the end of infusion (C inf) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Cumulative amount of a compound excreted in the urine (Ae)
Measured: only D1 of cycle 1
Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)
Measured: From first dose until 30 days after the last dose administration
Time corresponding to end of infusion (tinf/tend) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Time corresponding to Clast (tlast) in plasma.
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Last quantifiable observed concentration (Clast) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Area Under the Curve (AUC) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Terminal elimination half-life (t½,z) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
total Clearance (CL)
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Volume of distribution at steady-state (Vss) in plasma
Measured: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Ae expressed as a percentage of the dose (fe) in urine
Measured: only D1 of cycle 1
Renal clearance (CLR)
Measured: only D1 of cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2016 (estimated)
- Study start15 Mar 2017
- Primary completion11 May 2020
- Study completion11 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukaemia (AML)Studies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 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
- Investigators
- Andrew WEI, Principal investigator, The Alfred Hospital, Melbourne, Victoria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02979366
- Sponsor's protocol ID
- CL1-64315-001
- Other IDs
- 2016-003768-38, 136541, 2016
- Status last verified
- Mar 2021
- First submitted
- 18 Nov 2016
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- 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 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT02979366
- Acronym / sponsor ID
- CL1-64315-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Study start
- 15 Mar 2017 (actual)
- Primary completion
- 11 May 2020 (actual)
- Study completion
- 11 May 2020 (actual)
- First posted
- 1 Dec 2016 (estimated)
- 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 CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| S64315 (also referred as MIK665) administered once a week | Experimental | Drug: S64315 once a week |
| S64315 (also referred as MIK665) administered twice a week | Experimental | Drug: S64315 twice a week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female aged ≥ 18 years;
- Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Circulating white blood cells < 10^9 /L (with or without use of hydroxycarbamide).
- Adequate renal function defined as:
Key exclusion criteria (11 listed)
- Unlikely to cooperate in the study.
- Participant already enrolled in the study who has received at least one S64315 infusion.
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- Participation in another interventional study requiring investigational treatment intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first dose of S64315 (participation in non-interventional registries or epidemiological studies is allowed).
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03)
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 |
|---|---|---|
| S64315 once a weekAlso: MIK665S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours once every week (21- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed. | Drug | S64315 (also referred as MIK665) administered once a week |
| S64315 twice a weekAlso: MIK665S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours twice every week (28- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed. | Drug | S64315 (also referred as MIK665) administered twice a week |
Primary outcome
Incidence of DLTs during the first cycle of treatment with single agent S64315
Time frame: 21-day cycle 1
Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs
Time frame: From first dose until 30 days after the last dose administration
Tolerability: Dose interruptions
Time frame: From first dose until 30 days after the last dose administration
Tolerability: Dose reductions
Time frame: From first dose until 30 days after the last dose administration
Tolerability: Dose intensity
Time frame: From first dose until 30 days after the last dose administration
13 secondary outcomes
Concentration at the end of infusion (C inf) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Cumulative amount of a compound excreted in the urine (Ae)
Time frame: only D1 of cycle 1
Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)
Time frame: From first dose until 30 days after the last dose administration
Time corresponding to end of infusion (tinf/tend) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Time corresponding to Clast (tlast) in plasma.
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Last quantifiable observed concentration (Clast) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Area Under the Curve (AUC) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Terminal elimination half-life (t½,z) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
total Clearance (CL)
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Volume of distribution at steady-state (Vss) in plasma
Time frame: D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Ae expressed as a percentage of the dose (fe) in urine
Time frame: only D1 of cycle 1
Renal clearance (CLR)
Time frame: only D1 of cycle 1
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 2022.
- 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.
Andrew WEI principal investigator
The Alfred Hospital, Melbourne, Victoria
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing S64315 once a week and S64315 twice a week in people with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS), run by Institut de Recherches Internationales Servier at 9 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 14 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 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, United States, Australia, Spain. 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 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.
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?
Incidence of DLTs during the first cycle of treatment with single agent S64315 (time frame: 21-day cycle 1). The study lists 5 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 18 May 2022.