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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03755154




Registration number
NCT03755154
Ethics application status
Date submitted
13/11/2018
Date registered
27/11/2018

Titles & IDs
Public title
Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia
Scientific title
Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia
Secondary ID [1] 0 0
2018-004170-97
Secondary ID [2] 0 0
CL1-65487-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Acute Myeloid Leukemia 0 0
Relapsed or Refractory Non-Hodgkin Lymphoma 0 0
Relapsed or Refractory Multiple Myeloma 0 0
Relapsed or Refractory Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - S65487- initial scheme
Treatment: Drugs - S65487 - alternative scheme

Experimental: S65487 - initial scheme -

Experimental: S65487 - alternative scheme -


Treatment: Drugs: S65487- initial scheme
S65487 is administered as single agent via i.v. infusion once a week on a 3-week cycle.

Treatment: Drugs: S65487 - alternative scheme
S65487 is administered in 3 to 5 i.v. infusions the first week of each cycle then once a week on the rest of the 3-week cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
until the end of the first cycle (each cycle is 21days)
Primary outcome [2] 0 0
Incidence and severity of Adverse Events
Timepoint [2] 0 0
through study completion an average of 6 months
Primary outcome [3] 0 0
Incidence and severity of Serious Adverse Events
Timepoint [3] 0 0
through study completion an average of 6 months
Primary outcome [4] 0 0
Number of participants with dose reductions
Timepoint [4] 0 0
through study completion an average of 6 months
Primary outcome [5] 0 0
Number of participants with dose interruptions
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
The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC)
Timepoint [1] 0 0
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
Secondary outcome [2] 0 0
PK profile of S65487: Volume of distribution at steady-state (Vss)
Timepoint [2] 0 0
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
Secondary outcome [3] 0 0
PK profile of S65487: total CLearance (CL)
Timepoint [3] 0 0
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
Secondary outcome [4] 0 0
PK profile of S65487: terminal half-life (t½z)
Timepoint [4] 0 0
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
Secondary outcome [5] 0 0
Best Overall Response (BOR)
Timepoint [5] 0 0
Through study completion, an average of 6 months
Secondary outcome [6] 0 0
Overall Response Rate (ORR)
Timepoint [6] 0 0
Through study completion, an average of 6 months

Eligibility
Key inclusion criteria
* Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia with relapsed or refractory disease without established alternative therapy. Or patients with measurable confirmed Multiple Myeloma (IMWG) with relapsed or refractory disease who have previously received at least three lines of treatment and without established alternative therapy. Or patients with histologically and measurable confirmed Non Hodgkin Lymphoma defined as Diffuse Large B cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), High-Grade B cell Lymphoma with relapsed or refractory disease who have received at least two lines of therapy (including rituximab) and without established alternative therapy. Or patients with Chronic Lymphocytic Leukemia (CLL) who have relapsed or are refractory (except treatment failure), as defined per iwCLL, from venetoclax treatment and without established alternative therapy.
* ECOG (Eastern Cooperative Oncology Group) performance status = 2.
* For NHL, MM patients and CLL patients: haematological function (independent of any growth factor support) based on the last assessment performed before inclusion, defined as: absolute neutrophil count (ANC) = 1 x 109/L, haemoglobin = 8 g/dL, platelet count = 50 x 109/L for NHL and MM patients, platelet count = 30 x 109/L for CLL patients.
* For AML patients: circulating Blood White Cell count (WBC count) < 25 x 109/L (with or without use of hydroxycarbamide/leukapheresis) based on the last assessment performed before inclusion.
* Adequate renal function based on the last assessment performed before inclusion, assessed as Glomerular Filtration Rate (GFR) using Modification of Diet in Renal Disease (MDRD) Formula.
* Adequate hepatic function based on the last assessment performed before inclusion.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
* Participation in another interventional study at the same time or another interventional study requiring investigational treatment intake within 3 weeks or at least 5 half-lives (whichever is longer) prior to the first S65487 administration.
* Participant already enrolled in the study (informed consent signed) and has received at least one dose of S65487.
* Patients who have not recovered from toxicity of previous anticancer therapy, including grade = 2 non-hematologic toxicity, prior to the first IMP administration (including peripheral neurotoxicity). Certain toxicities will not be considered in this category (e.g. alopecia).
* Patients refractory to a previous treatment with a Bcl-2 inhibitor.
* For AML patients : Allogenic stem cell transplant within 3 months before the first IMP administration and/or patients who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or patients with active Graft-versus-host disease within 3 months before the first IMP administration and/or patient who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration.
* For NHL, MM and CLL patients : Prior allogenic stem cell transplant before the first IMP administration and/or Autologous stem cell transplant within 3 months before the first IMP administration.

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
Parallel
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
17/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/11/2023
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Lille
Country [2] 0 0
France
State/province [2] 0 0
Nantes
Country [3] 0 0
France
State/province [3] 0 0
Nice
Country [4] 0 0
Spain
State/province [4] 0 0
Madrid
Country [5] 0 0
Spain
State/province [5] 0 0
Pamplona
Country [6] 0 0
Spain
State/province [6] 0 0
Salamanca
Country [7] 0 0
Spain
State/province [7] 0 0
Valencia
Country [8] 0 0
United Kingdom
State/province [8] 0 0
London
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Manchester
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Newcastle

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?

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/NCT03755154