Multiple Myeloma (MM) Clinical Trial
Official title:
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
Verified date | November 2019 |
Source | Servier |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Institut de Recherches Internationales Servier | ADIR, a Servier Group company |
Australia, France, Germany, Hungary, Korea, Republic of, Poland, Singapore, United Kingdom,
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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