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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04629443




Registration number
NCT04629443
Ethics application status
Date submitted
3/11/2020
Date registered
16/11/2020

Titles & IDs
Public title
Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia
Scientific 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)
Secondary ID [1] 0 0
2019-004896-38
Secondary ID [2] 0 0
CL1-64315-004
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
Treatment: Drugs - S 64315 (also referred as MIK665) and azacitidine

Experimental: S64315 (also referred as MIK665) with azacitidine -


Treatment: Drugs: S 64315 (also referred as MIK665) and azacitidine
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)
Timepoint [1] 0 0
Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
Primary outcome [2] 0 0
Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
Timepoint [2] 0 0
an average of 6 months
Primary outcome [3] 0 0
Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)
Timepoint [3] 0 0
Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)
Primary outcome [4] 0 0
Number of Participants With Dose Interruptions (Phase I - Dose Escalation)
Timepoint [4] 0 0
Through study completion, an average of 6 months
Primary outcome [5] 0 0
Number of Participants With Dose Reductions (Phase I - Dose Escalation)
Timepoint [5] 0 0
Through study completion, an average of 6 months
Primary outcome [6] 0 0
Dose Intensity for S64315 (Phase I - Dose Escalation)
Timepoint [6] 0 0
Through study completion, an average of 6 months
Primary outcome [7] 0 0
Dose Intensity for Azacitidine (Phase I - Dose Escalation)
Timepoint [7] 0 0
Through study completion, an average of 6 months
Secondary outcome [1] 0 0
Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)
Timepoint [1] 0 0
Through study completion, an average of 6 months
Secondary outcome [2] 0 0
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Timepoint [2] 0 0
Through study completion, an average of 6 months
Secondary outcome [3] 0 0
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Timepoint [3] 0 0
Through study completion, an average of 6 months
Secondary outcome [4] 0 0
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Timepoint [4] 0 0
Through study completion, an average of 6 months
Secondary outcome [5] 0 0
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
Timepoint [5] 0 0
Through study completion, an average of 6 months
Secondary outcome [6] 0 0
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)
Timepoint [6] 0 0
At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Secondary outcome [7] 0 0
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)
Timepoint [7] 0 0
At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)

Eligibility
Key inclusion criteria
1. Patients aged = 18 years
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
4. Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous myeloproliferative syndrome (MPS).
2. Patients previously treated with any Mcl-1 inhibitor.
3. 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.
4. Severe or uncontrolled active acute or chronic infection.
5. Uncontrolled hepatitis B or C infection.
6. Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
7. Troponin > ULN (Upper Limit of reference range) or Troponin T > ULN if Troponin I cannot be assessed.
8. 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).
9. 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.
10. 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.
11. Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
17/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/08/2023
Sample size
Target
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Victorian Comprehensive Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
France
State/province [2] 0 0
Marseille
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Spain
State/province [4] 0 0
Barcelona
Country [5] 0 0
Spain
State/province [5] 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
Address 0 0
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?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04629443