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Acute Myeloid Leukaemia (AML)Phase 1NCT02920541

Dose-escalation Study of Oral Administration of S 055746 in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome

A Phase 1 study testing S 055746 in people with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS), run by Institut de Recherches Internationales Servier at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the safety profile and tolerability of S 055746 in patients with AML, and high or very high risk MDS, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
S 055746
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
5 sitesin 2 countries
Study dates
Jan 2015to 24 May 2018
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

  • Women or men aged >= 18 years
  • Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML excluding acute promyelocytic leukaemia:
  • with relapsed or refractory disease or
  • > or = 65 years not previously treated for AML, who are not candidates for intensive chemotherapy or not candidates for standard chemotherapy
  • Patients with cytologically confirmed and documented MDS or non proliferative Chronic Myelomonocytic Leukaemia (CMML) in relapse or refractory after previous treatment line including at least one hypomethylating agent therapy:
  • with high or very high risk MDS and without established alternative therapy
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  • transformed to AML and without established alternative therapy
  • Ability to swallow oral tablet(s)
  • World Health Organization (WHO) performance status 0-2
  • Circulating white blood cells < or = 30 x 10^9 /L and < or = 13 x10^9 for non proliferative CMML
  • Adequate renal and hepatic functions
  • Negative serum pregnancy test within 7 days prior to the first day of study drug administration
  • Patients must use effective contraception
  • Written informed consent

Who cannot join

  • Foreseeable poor compliance to the study procedures
  • Legally incapacitated person under guardianship or trusteeship
  • Pregnant or breast-feeding women
  • Participation in therapeutic interventional study involving investigational drug intake at the same time or within 2 weeks or at least 5 half-lives or patient already enrolled
  • Previous treatment with a BH3 mimetic
  • Patients who have not recovered to baseline or CTCAE< or = Grade 1 from toxicity due to all prior therapies received for the studied disease
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  • Any previous anti-leukaemic treatment for the studied disease within at least 5 half-lives or 2 weeks (hydroxycarbamide permitted)
  • Any radiotherapy within 4 weeks before first intake (except palliative radiotherapy at localized lesions)
  • Major surgery within 3 weeks before first intake of S 055746
  • Allogenic stem cell transplant within 6 months before the first intake of S 055746 and for patients who still need immunosuppressive treatment
  • Leukaemic leptomeningeal or leukaemic central nervous system involvement
  • Concomitant uncontrolled infection, organ dysfunction or medical disease likely to interfere with evaluation of S 055746 safety or study outcome
  • Human immunodeficiency virus (HIV) infection, hepatitis B or active hepatitis C infection
  • Within 6 months prior to the first intake of S 055746, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, and/or stenting, ischemic/haemorrhagic stroke, atrial fibrillation, digestive haemorrhagic risk, deep venous/arterial thromboembolic complication or bleeding diathesis
  • Decreased Left Ventricular Ejection Fraction (LVEF)
  • QTcF prolongation
  • Patients who are receiving QT prolonging drug
  • Coagulopathies with increased risk of bleeding complications
  • Other malignancy within 2 years prior to the first intake
  • Strong or moderate CYP3A4 inhibitors or inducers (treatment, food or drink products) within 7 days prior to the first intake
  • Treatment highly metabolised by the CYP3A4 or CYP2D6 and/or with a narrow therapeutic index, multi-enzymes and/or OATP and/or P-gp substrates or herbal products within 7 days prior to the first intake.
  • Patients receiving proton pump inhibitor
  • Patients having received anticoagulant oral drugs, aspirin > 325 mg/day and antiplatelets within 7 days prior to first S 055746 intake

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

France3 sites

  • Institut Paoli Calmettes

    Marseille

  • Hôpital Saint Louis

    Paris

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite

Other trials in France

Australia2 sites

  • The Alfred Hospital

    Melbourne

  • Royal Melbourne Hospital

    Parkville

Other trials in Australia

About this study

Official title: Phase I Dose-escalation Study of the Orally Administered Selective Bcl-2 Inhibitor S 055746 as Monotherapy for the Treatment of Patients With Acute Myeloid Leukaemia (AML) or High or Very High Risk Myelodysplastic Syndrome (MDS)

The purpose of this study is to determine the safety profile and tolerability of S 055746 in patients with AML, and high or very high risk MDS, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD profile and preliminary efficacy.

Being tested
S 055746
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.

  • S 055746Drug

    S 055746, per os administration, from 50 to 2000 mg once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Study groups in NCT02920541
Study groupRoleWhat they receive
S 055746ExperimentalNot described
Receives: Drug: S 055746

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    MTD is the highest drug dosage that is unlikely (<25% posterior probability) to cause DLT in more than 33% of the treated patients in the first cycle of S 055746 treatment.

    Measured: During cycle 1 (21 days)

  2. Incidence of Adverse Events (AEs)

    Characterized by severity and seriousness of AEs, laboratory abnormalities and other safety parameters such as electrocardiogram (ECG) changes

    Measured: From first dose until 30 days after the last dose intake

Secondary outcomes (6)

  1. Plasma concentration of S 055746

    Measured: Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8

  2. The pharmacokinetic (PK) profile of S 055746: Area Under the Curve [AUC]

    Measured: Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8

  3. The PK profile of S 055746: Maximal Concentration [Cmax]

    Measured: Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8

  4. Best Response Rate (BRR)

    Measured: Up to study completion (maximum of 3 years)

  5. Progression Free Survival (PFS)

    Measured: From date of inclusion until the date of progression or date of death, whichever occurs first, assessed up to study completion (maximum of 3 years)

  6. Event Free Survival (EFS)

    Measured: From date of inclusion until the date of progression or date of death or discontinuation of treatment, whichever occurs first, assessed up to study completion (maximum of 3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2016 (estimated)
  2. Study startJan 2015
  3. Primary completion24 May 2018
  4. Study completion24 May 2018

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02920541
Sponsor's protocol ID
CL1-055746-002
Other IDs
2014-002559-24, ISRCTN73586707, 2014
Status last verified
May 2019
First submitted
23 Aug 2016
Last updated
24 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs). They can ask all interventional clinical studies: * submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing S 055746 in people with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS), run by Institut de Recherches Internationales Servier at 5 sites in 2 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 23 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 24 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France, Australia. 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?

Maximum Tolerated Dose (MTD) (time frame: During cycle 1 (21 days)). The study lists 2 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 NCT02920541.

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 24 May 2019.

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