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

NCT ID: NCT02920697

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2018-10-22

Brief 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)

Group Type: EXPERIMENTAL

S 55746

Intervention Type: DRUG

S 55746, per os administration, from 50 to 1500 mg, once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Chronic Lymphocytic Leukaemia (CLL)

Group Type: EXPERIMENTAL

S 55746

Intervention Type: DRUG

S 55746, per os administration, from 50 to 1500 mg, once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Interventions

S 55746

S 55746, per os administration, from 50 to 1500 mg, once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Intervention Type: DRUG

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Le Gouill, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services

Melbourne, , Australia

Hopital Claude Huriez

Lille, , France

CHU de Nantes

Nantes, , France

Centre hospitalier Lyon Sud

Pierre-Bénite, , France

Gustave Roussy

Villejuif, , France

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Städtisches Klinikum Schwabing

Munich, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

National Oncology Institute

Budapest, , Hungary

CRU Hungary Kft

Miskolc, , Hungary

Warsaw Institute of Oncology

Warsaw, , Poland

Warsaw Medical University

Warsaw, , Poland

National Cancer Center (NCC)

Singapore, , Singapore

National University Cancer Institute Singapore

Singapore, , Singapore

Severance Hospital

Seoul, , South Korea

St. Mary's Hospital

Seoul, , South Korea

University College London Hospitals

London, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Countries

Australia; France; Germany; Hungary; Poland; Singapore; South Korea; United Kingdom

References

Le Gouill S, Wermke M, Morschhauser F, Lim ST, Salles G, Kloos I, de Burgat V, Becquart M, Paux G, Kraus-Berthier L, Pennaforte S, Stilgenbauer S, Walewski J, Ribrag V. A new BCL-2 Inhibitor (S55746/BCL201) as Monotherapy in Patients with Relapsed or Refractory Non-hodgkin Lymphoma: Preliminary Results of the First-in-human Study. Hematol Oncol. 2017 Jun 07;35(S5):14-17. doi: 10.1002/hon.2437_30

Reference Type: BACKGROUND

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: study-level clinical trial data

View Document

Document Type: Clinical Study Report

View Document

Other Identifiers

2013-003779-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN04804337

Identifier Type: REGISTRY

Identifier Source: secondary_id

CL1-55746-001

Identifier Type: -

Identifier Source: org_study_id