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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02920697
Other study ID # CL1-55746-001
Secondary ID 2013-003779-36IS
Status Completed
Phase Phase 1
First received
Last updated
Start date March 2014
Est. completion date October 22, 2018

Study information

Verified date November 2019
Source Servier
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 65
Est. completion date October 22, 2018
Est. primary completion date October 22, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

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


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Australia The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services Melbourne
France Hopital Claude Huriez Lille
France CHU de Nantes Nantes
France Centre hospitalier Lyon Sud Pierre-Bénite
France Gustave Roussy Villejuif
Germany Universitätsklinikum Carl Gustav Carus Dresden
Germany Städtisches Klinikum Schwabing Munich
Germany Universitätsklinikum Ulm Ulm
Hungary National Oncology Institute Budapest
Hungary CRU Hungary Kft Miskolc
Korea, Republic of Severance Hospital Seoul
Korea, Republic of St. Mary's Hospital Seoul
Poland Warsaw Institute of Oncology Warsaw
Poland Warsaw Medical University Warsaw
Singapore National Cancer Center (NCC) Singapore
Singapore National University Cancer Institute Singapore Singapore
United Kingdom University College London Hospitals London
United Kingdom Freeman Hospital Newcastle

Sponsors (2)

Lead Sponsor Collaborator
Institut de Recherches Internationales Servier ADIR, a Servier Group company

Countries where clinical trial is conducted

Australia,  France,  Germany,  Hungary,  Korea, Republic of,  Poland,  Singapore,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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)
Primary 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 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
Secondary 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
Secondary 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
Secondary Apoptotic activity from blood samples At Cycle 1(21 days)
Secondary Objective Response Rate (ORR) Up to study completion (maximum of 3 years)
Secondary Clinical Benefit Rate (CBR) Up to study completion (maximum of 3 years)
Secondary Duration of response Up to study completion (maximum of 3 years)
Secondary 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)
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