dose-escalation study of oral administration of s 55746 in patients with chronic lymphocytic leukaemia and b-cell non-hodgkin lymphoma

Conditions: Chronic Lymphocytic Leukaemia (CLL); B-Cell Non-Hodgkin Lymphoma (NHL); Multiple Myeloma (MM)

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.


Eligibility 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