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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02920697




Registration number
NCT02920697
Ethics application status
Date submitted
23/08/2016
Date registered
30/09/2016

Titles & IDs
Public title
Dose-escalation Study of Oral Administration of S 55746 in Patients With Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma
Scientific title
Phase I Dose-escalation Study of Oral Administration of the Selective Bcl2 Inhibitor S 55746 in Patients With Refractory or Relapsed Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
2013-003779-36
Secondary ID [2] 0 0
CL1-55746-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukaemia (CLL) 0 0
B-Cell Non-Hodgkin Lymphoma (NHL) 0 0
Multiple Myeloma (MM) 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 - S 55746

Experimental: B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) -

Experimental: Chronic Lymphocytic Leukaemia (CLL) -


Treatment: Drugs: S 55746
S 55746, per os administration, from 50 to 1500 mg, once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
During cycle 1 (21 days)
Primary outcome [2] 0 0
Incidence of Adverse Events (AEs)
Timepoint [2] 0 0
From first dose until 30 days after the last dose intake
Secondary outcome [1] 0 0
Plasma concentration of S 55746
Timepoint [1] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [2] 0 0
The pharmacokinetic (PK) profile of S 55746: Area Under the Curve [AUC]
Timepoint [2] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [3] 0 0
The PK profile of S 55746: Maximal Concentration [Cmax]
Timepoint [3] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [4] 0 0
Apoptotic activity from blood samples
Timepoint [4] 0 0
At Cycle 1(21 days)
Secondary outcome [5] 0 0
Objective Response Rate (ORR)
Timepoint [5] 0 0
Up to study completion (maximum of 3 years)
Secondary outcome [6] 0 0
Clinical Benefit Rate (CBR)
Timepoint [6] 0 0
Up to study completion (maximum of 3 years)
Secondary outcome [7] 0 0
Duration of response
Timepoint [7] 0 0
Up to study completion (maximum of 3 years)
Secondary outcome [8] 0 0
Progression Free Survival (PFS)
Timepoint [8] 0 0
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)

Eligibility
Key inclusion criteria
* Women or men aged >/=18 years
* Patients with a measurable histologically confirmed Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Diffuse Large B-Cell Lymphoma (DLBCL), Small Lymphocytic Lymphoma (SLL) and Marginal Zone Lymphoma (MZL) (Arm A), or patients with an evaluable immunophenotypically confirmed CLL (Arm B), or patients with a measurable Multiple Myeloma t(11;14) (arm A expansion part) according to International Myeloma Working Group (IMWG) criteria
* Relapsed after or refractory disease to standard treatments, and require treatment in the opinion of the investigator
* Estimated life expectancy > 12 weeks
* World Health Organization (WHO) performance status 0-2
* Adequate bone marrow, renal and hepatic functions
* No evidence or treatment for another malignancy within 2 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed

Additional inclusion criteria for food interaction cohort:

* B-cell NHL patients at low risk of tumour lysis syndrome (TLS)
* Recent/concomitant treatment altering gastric pH
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with a BH3 mimetic
* Previous therapy for the studied disease within 3 weeks before first intake
* Radioimmunotherapy, radiotherapy within 8 weeks before first intake
* Major surgery within 3 weeks before first day of study drug dosing
* Corticosteroids >= 20 mg prednisone equivalent per day within 7 days before first intake
* Anticoagulant oral drugs, aspirin > 325 mg/day within 7 days prior to first S 55746 intake
* Positive direct antiglobulin test (Coombs test) and haptoglobin below normal value
* Prior allogenic stem cell transplant
* Autologous stem cell transplant within 3 months before first intake
* NHL patients diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukaemia
* Human immunodeficiency virus (HIV)
* Known acute or chronic hepatitis B or hepatitis C
* Impaired cardiac function
* Medications known to prolong corrected QT (QTc) interval
* History or/ clinically suspicious for cancer- related Central Nervous System disease
* Solitary extramedullary plasmacytoma
* Laboratory Signs of TLS
* Strong or moderate CYP3A4 inhibitors/inducers (treatment, food or drink products)
* Treatment highly metabolized by the CYP3A4 or CYP2D6 and/or substrates with a narrow therapeutic index, multienzyme and/or OATP and/or P-gp substrates or herbal products.
* Known hypersensitivity to rasburicase
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency and other cellular metabolic disorders known to cause haemolytic anaemia
* Patients receiving proton pump inhibitor

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
1/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/10/2018
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
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
Pierre-Bénite
Country [4] 0 0
France
State/province [4] 0 0
Villejuif
Country [5] 0 0
Germany
State/province [5] 0 0
Dresden
Country [6] 0 0
Germany
State/province [6] 0 0
Munich
Country [7] 0 0
Germany
State/province [7] 0 0
Ulm
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Hungary
State/province [9] 0 0
Miskolc
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Poland
State/province [11] 0 0
Warsaw
Country [12] 0 0
Singapore
State/province [12] 0 0
Singapore
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London
Country [14] 0 0
United Kingdom
State/province [14] 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
Steven Le Gouill, M.D., Ph.D.
Address 0 0
Nantes University Hospital
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?
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.

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: http://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/NCT02920697