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

• Status: Completed
• Trial end date: 2018-10-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

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