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

July 24, 2024 updated by: Institut de Recherches Internationales Servier

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
65

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Melbourne, Australia, 3004
        • The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
  • France
      • Lille, France
        • Hopital Claude Huriez
      • Nantes, France
        • CHU de Nantes
      • Pierre-Bénite, France
        • Centre Hospitalier Lyon Sud
      • Villejuif, France
        • Gustave Roussy
  • Germany
      • Dresden, Germany
        • Universitatsklinikum Carl Gustav Carus
      • Munich, Germany
        • Städtisches Klinikum Schwabing
      • Ulm, Germany
        • Universitätsklinikum Ulm
  • Hungary
      • Budapest, Hungary
        • National Oncology Institute
      • Miskolc, Hungary
        • CRU Hungary Kft
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Severance Hospital
      • Seoul, Korea, Republic of
        • St. Mary's Hospital
  • Poland
      • Warsaw, Poland
        • Warsaw Institute of Oncology
      • Warsaw, Poland
        • Warsaw Medical University
  • Singapore
      • Singapore, Singapore
        • National Cancer Center (NCC)
      • Singapore, Singapore
        • National University Cancer Institute Singapore
  • United Kingdom
      • London, United Kingdom
        • University College London Hospitals
      • Newcastle, United Kingdom
        • Freeman Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)
Drug: 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.
Experimental: Chronic Lymphocytic Leukaemia (CLL)
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: During cycle 1 (21 days)
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)
Incidence of Adverse Events (AEs)
Time Frame: From first dose until 30 days after the last dose intake
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Plasma concentration of S 55746
Time Frame: 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
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
The pharmacokinetic (PK) profile of S 55746: Area Under the Curve [AUC]
Time Frame: 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
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
The PK profile of S 55746: Maximal Concentration [Cmax]
Time Frame: 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
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
Apoptotic activity from blood samples
Time Frame: At Cycle 1(21 days)
At Cycle 1(21 days)
Objective Response Rate (ORR)
Time Frame: Up to study completion (maximum of 3 years)
Up to study completion (maximum of 3 years)
Clinical Benefit Rate (CBR)
Time Frame: Up to study completion (maximum of 3 years)
Up to study completion (maximum of 3 years)
Duration of response
Time Frame: Up to study completion (maximum of 3 years)
Up to study completion (maximum of 3 years)
Progression Free Survival (PFS)
Time Frame: 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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut de Recherches Internationales Servier

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ADIR, a Servier Group company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steven Le Gouill, M.D., Ph.D., Nantes University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 22, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 22, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 30, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 25, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CL1-55746-001
  • 2013-003779-36 (EudraCT Number)
  • ISRCTN04804337 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

IPD Sharing Time Frame

After Marketing Authorisation in EEA or US if the study is used for the approval.

IPD Sharing Access Criteria

Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Study Data/Documents

  1. Individual Participant Data Set
  2. Study Protocol
  3. Statistical Analysis Plan
  4. Informed Consent Form
  5. Clinical Study Report
  6. study-level clinical trial data

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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