Dose-escalation Study of Oral Administration of S 55746 in Patients With Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma
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
3 other identifiers
interventional
65
8 countries
18
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2014
CompletedFirst Submitted
Initial submission to the registry
August 23, 2016
CompletedFirst Posted
Study publicly available on registry
September 30, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 22, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 22, 2018
CompletedJuly 25, 2024
July 1, 2024
4.6 years
August 23, 2016
July 24, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD)
The MTD is the highest drug dosage that is unlikely (\<25% posterior probability) to cause DLT in more than 33% of the treated patients in the first cycle of S 55746 treatment
During cycle 1 (21 days)
Incidence of Adverse Events (AEs)
Characterized by severity and seriousness of AEs, laboratory abnormalities and other safety parameters such as electrocardiogram (ECG) changes
From first dose until 30 days after the last dose intake
Secondary Outcomes (8)
Plasma concentration of S 55746
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
The pharmacokinetic (PK) profile of S 55746: Area Under the Curve [AUC]
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
The PK profile of S 55746: Maximal Concentration [Cmax]
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
Apoptotic activity from blood samples
At Cycle 1(21 days)
Objective Response Rate (ORR)
Up to study completion (maximum of 3 years)
- +3 more secondary outcomes
Study Arms (2)
B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)
EXPERIMENTALChronic Lymphocytic Leukaemia (CLL)
EXPERIMENTALInterventions
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.
Eligibility Criteria
You may qualify if:
- 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
- B-cell NHL patients at low risk of tumour lysis syndrome (TLS)
- Recent/concomitant treatment altering gastric pH
You may not qualify if:
- 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
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
Melbourne, 3004, Australia
Hopital Claude Huriez
Lille, France
CHU de Nantes
Nantes, France
Centre hospitalier Lyon Sud
Pierre-Bénite, France
Gustave Roussy
Villejuif, France
Universitätsklinikum Carl Gustav Carus
Dresden, Germany
Städtisches Klinikum Schwabing
Munich, Germany
Universitätsklinikum Ulm
Ulm, Germany
National Oncology Institute
Budapest, Hungary
CRU Hungary Kft
Miskolc, Hungary
Warsaw Institute of Oncology
Warsaw, Poland
Warsaw Medical University
Warsaw, Poland
National Cancer Center (NCC)
Singapore, Singapore
National University Cancer Institute Singapore
Singapore, Singapore
Severance Hospital
Seoul, South Korea
St. Mary's Hospital
Seoul, South Korea
University College London Hospitals
London, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Related Publications (1)
Le Gouill S, Wermke M, Morschhauser F, Lim ST, Salles G, Kloos I, de Burgat V, Becquart M, Paux G, Kraus-Berthier L, Pennaforte S, Stilgenbauer S, Walewski J, Ribrag V. A new BCL-2 Inhibitor (S55746/BCL201) as Monotherapy in Patients with Relapsed or Refractory Non-hodgkin Lymphoma: Preliminary Results of the First-in-human Study. Hematol Oncol. 2017 Jun 07;35(S5):14-17. doi: 10.1002/hon.2437_30
BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Steven Le Gouill, M.D., Ph.D.
Nantes University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2016
First Posted
September 30, 2016
Study Start
March 1, 2014
Primary Completion
October 22, 2018
Study Completion
October 22, 2018
Last Updated
July 25, 2024
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorisation in EEA or US if the study is used for the approval.
- Access Criteria
- 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.
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.