Dose-escalation Study of Oral Administration of S 55746 in Patients With Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma
- Conditions
- Multiple Myeloma (MM)Chronic Lymphocytic Leukaemia (CLL)B-Cell Non-Hodgkin Lymphoma (NHL)
- Interventions
- Drug: S 55746
- Registration Number
- NCT02920697
- Lead Sponsor
- Institut de Recherches Internationales Servier
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Chronic Lymphocytic Leukaemia (CLL) S 55746 - B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) S 55746 -
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) During cycle 1 (21 days) 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
Incidence of Adverse Events (AEs) From first dose until 30 days after the last dose intake Characterized by severity and seriousness of AEs, laboratory abnormalities and other safety parameters such as electrocardiogram (ECG) changes
- Secondary Outcome Measures
Name Time Method Apoptotic activity from blood samples At Cycle 1(21 days) Objective Response Rate (ORR) Up to study completion (maximum of 3 years) 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 Progression Free Survival (PFS) 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) 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 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 Clinical Benefit Rate (CBR) Up to study completion (maximum of 3 years) Duration of response Up to study completion (maximum of 3 years)
Trial Locations
- Locations (18)
National University Cancer Institute Singapore
🇸🇬Singapore, Singapore
CRU Hungary Kft
🇭🇺Miskolc, Hungary
Warsaw Medical University
🇵🇱Warsaw, Poland
National Cancer Center (NCC)
🇸🇬Singapore, Singapore
Warsaw Institute of Oncology
🇵🇱Warsaw, Poland
National Oncology Institute
🇭🇺Budapest, Hungary
St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
CHU de Nantes
🇫🇷Nantes, France
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
🇦🇺Melbourne, Australia
Hopital Claude Huriez
🇫🇷Lille, France
Centre hospitalier Lyon Sud
🇫🇷Pierre-Bénite, France
Gustave Roussy
🇫🇷Villejuif, France
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Städtisches Klinikum Schwabing
🇩🇪Munich, Germany
University College London Hospitals
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom