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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02920697




Registration number
NCT02920697
Ethics application status
Date submitted
23/08/2016
Date registered
30/09/2016
Date last updated
25/11/2019

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
The purpose of this study is to determine the safety profile and tolerability of S 55746 in
patients with CLL, B-Cell NHL and MM, in terms of Dose-Limiting Toxicities (DLTs), Maximum
Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile
(DLT, MTD), PK profile, PD profile and preliminary efficacy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02920697
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02920697