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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02979366




Registration number
NCT02979366
Ethics application status
Date submitted
18/11/2016
Date registered
1/12/2016

Titles & IDs
Public title
Phase I Study of S64315 Administred Intravenously in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome
Scientific 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)
Secondary ID [1] 0 0
2016-003768-38
Secondary ID [2] 0 0
CL1-64315-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia (AML) 0 0
Myelodysplastic Syndrome (MDS) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - S64315 once a week
Treatment: Drugs - S64315 twice a week

Experimental: S64315 (also referred as MIK665) administered once a week -

Experimental: S64315 (also referred as MIK665) administered twice a week -


Treatment: Drugs: S64315 once a week
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.

Treatment: Drugs: S64315 twice a week
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of DLTs during the first cycle of treatment with single agent S64315
Timepoint [1] 0 0
21-day cycle 1
Primary outcome [2] 0 0
Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs
Timepoint [2] 0 0
From first dose until 30 days after the last dose administration
Primary outcome [3] 0 0
Tolerability: Dose interruptions
Timepoint [3] 0 0
From first dose until 30 days after the last dose administration
Primary outcome [4] 0 0
Tolerability: Dose reductions
Timepoint [4] 0 0
From first dose until 30 days after the last dose administration
Primary outcome [5] 0 0
Tolerability: Dose intensity
Timepoint [5] 0 0
From first dose until 30 days after the last dose administration
Secondary outcome [1] 0 0
Concentration at the end of infusion (C inf) in plasma
Timepoint [1] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [2] 0 0
Cumulative amount of a compound excreted in the urine (Ae)
Timepoint [2] 0 0
only D1 of cycle 1
Secondary outcome [3] 0 0
Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)
Timepoint [3] 0 0
From first dose until 30 days after the last dose administration
Secondary outcome [4] 0 0
Time corresponding to end of infusion (tinf/tend) in plasma
Timepoint [4] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [5] 0 0
Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma
Timepoint [5] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [6] 0 0
Time corresponding to Clast (tlast) in plasma.
Timepoint [6] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [7] 0 0
Last quantifiable observed concentration (Clast) in plasma
Timepoint [7] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [8] 0 0
Area Under the Curve (AUC) in plasma
Timepoint [8] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [9] 0 0
Terminal elimination half-life (t½,z) in plasma
Timepoint [9] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [10] 0 0
total Clearance (CL)
Timepoint [10] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [11] 0 0
Volume of distribution at steady-state (Vss) in plasma
Timepoint [11] 0 0
D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Secondary outcome [12] 0 0
Ae expressed as a percentage of the dose (fe) in urine
Timepoint [12] 0 0
only D1 of cycle 1
Secondary outcome [13] 0 0
Renal clearance (CLR)
Timepoint [13] 0 0
only D1 of cycle 1

Eligibility
Key inclusion criteria
* 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
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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)
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/05/2020
Sample size
Target
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Alfred Hospital Department of Haematology - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital, Department of Clinical Haematology and BMT Service - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
France
State/province [3] 0 0
Marseille
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
France
State/province [5] 0 0
Toulouse
Country [6] 0 0
Spain
State/province [6] 0 0
Barcelona
Country [7] 0 0
Spain
State/province [7] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Other
Name
Institut de Recherches Internationales Servier
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ADIR, a Servier Group company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andrew WEI
Address 0 0
The Alfred Hospital, Melbourne, Victoria
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorisation in EEA or US if the study is used for the approval.
Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://clinicaltrials.servier.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02979366