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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03672695




Registration number
NCT03672695
Ethics application status
Date submitted
4/09/2018
Date registered
14/09/2018

Titles & IDs
Public title
Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.
Scientific title
An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).
Secondary ID [1] 0 0
2018-001809-88
Secondary ID [2] 0 0
CL1-64315-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - S 64315 (also referred as MIK665) and venetoclax

Experimental: Initial Schedule - S64315 low dose and venetoclax high dose administered in combination -

Experimental: Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination -

Experimental: Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination -

Experimental: Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination -

Experimental: Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination -

Experimental: Alternative Schedule - Venetoclax medium dose administered with no S64315 -

Experimental: Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination -

Experimental: Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination -


Other interventions: S 64315 (also referred as MIK665) and venetoclax
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.

S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.

Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicity (DLTs)
Timepoint [1] 0 0
At the end of cycle 1 (each cycle is 21 or 28 days).
Primary outcome [2] 0 0
Incidence and severity of AEs
Timepoint [2] 0 0
Through study completion, an average of 6 months.
Primary outcome [3] 0 0
Incidence and severity of SAEs
Timepoint [3] 0 0
Through study completion, an average of 6 months.
Primary outcome [4] 0 0
Number of participants with dose interruptions "will be measured and reported in the Outcome Measure results data table.
Timepoint [4] 0 0
Through study completion, an average of 6 months.
Primary outcome [5] 0 0
Number of participants with dose reductions "will be measured and reported in the Outcome Measure results data table.
Timepoint [5] 0 0
Through study completion, an average of 6 months.
Primary outcome [6] 0 0
Dose intensity
Timepoint [6] 0 0
Through study completion, an average of 6 months.
Secondary outcome [1] 0 0
Anti-leukemic activity
Timepoint [1] 0 0
Through study completion, an average of 6 months.
Secondary outcome [2] 0 0
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC)
Timepoint [2] 0 0
From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Secondary outcome [3] 0 0
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf)
Timepoint [3] 0 0
From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Secondary outcome [4] 0 0
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z)
Timepoint [4] 0 0
From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).

Eligibility
Key inclusion criteria
1. Male or female aged = 18 years;
2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), 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 and without established alternative therapy or
* = 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative therapy
3. Eastern Cooperative Oncology Group (ECOG) performance status = 2
4. Able to comply with study procedures
5. Adequate renal function within 7 days before the inclusion of the patient defined as:

• Serum creatinine = 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2
6. Adequate hepatic function within 7 days before the inclusion of the patient defined as:

* AST and ALT = 1.5 x ULN
* Total serum bilirubin level = 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participant already enrolled and treated in the study
2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study
3. Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
4. 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 (NCICTCAE, version 4.03).
5. Known carriers of HIV antibodies
6. Known history of significant liver disease
7. Uncontrolled hepatitis B or C infection
8. Known active acute or chronic pancreatitis
9. History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
10. Any factors that could increase the risk of QTc prolongation or risk of arrhythmic events.

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
Other
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
28/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2023
Sample size
Target
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum cancer centrer - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital Department of Haematology - Victoria Park
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Victoria Park
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

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/NCT03672695