Dose-escalation Study of Oral Administration of S 55746 in Patients With Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma

Servier

Status and phase

Completed

Phase 1

Conditions

Chronic Lymphocytic Leukaemia (CLL)

Multiple Myeloma (MM)

B-Cell Non-Hodgkin Lymphoma (NHL)

Treatments

Drug: S 55746

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02920697

ISRCTN04804337 (Registry Identifier)

2013-003779-36 (EudraCT Number)

CL1-55746-001

Details and patient eligibility

About

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.

Enrollment

65 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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