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

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.

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