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Chronic Lymphocytic Leukaemia (CLL)Phase 1NCT02920697

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

A Phase 1 study testing S 55746 in people with Chronic Lymphocytic Leukaemia (CLL) and B-Cell Non-Hodgkin Lymphoma (NHL), run by Institut de Recherches Internationales Servier at 18 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
S 55746
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
18 sitesin 8 countries
Study dates
Mar 2014to 22 Oct 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

18 sites in 8 countries.

18 sites in 8 countries

France4 sites

  • Hopital Claude Huriez

    Lille

  • CHU de Nantes

    Nantes

  • Centre hospitalier Lyon Sud

    Pierre-Bénite

  • Gustave Roussy

    Villejuif

Other trials in France

Germany3 sites

  • Universitätsklinikum Carl Gustav Carus

    Dresden

  • Städtisches Klinikum Schwabing

    Munich

  • Universitätsklinikum Ulm

    Ulm

Other trials in Germany

Hungary2 sites

  • National Oncology Institute

    Budapest

  • CRU Hungary Kft

    Miskolc

Other trials in Hungary

Poland2 sites

  • Warsaw Institute of Oncology

    Warsaw

  • Warsaw Medical University

    Warsaw

Other trials in Poland

Singapore2 sites

  • National Cancer Center (NCC)

    Singapore

  • National University Cancer Institute Singapore

    Singapore

Other trials in Singapore

South Korea2 sites

  • Severance Hospital

    Seoul

  • St. Mary's Hospital

    Seoul

Other trials in South Korea

United Kingdom2 sites

  • University College London Hospitals

    London

  • Freeman Hospital

    Newcastle

Other trials in United Kingdom

Australia1 site

  • The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services

    Melbourne, 3004

Other trials in Australia

About this study

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

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.

Being tested
S 55746
Medical subject headings
Leukemia, B-Cell, Lymphoma, B-Cell, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • S 55746Drug

    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.

Study groups in NCT02920697
Study groupRoleWhat they receive
B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)ExperimentalNot described
Receives: Drug: S 55746
Chronic Lymphocytic Leukaemia (CLL)ExperimentalNot described
Receives: Drug: S 55746

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: During cycle 1 (21 days)

  2. Incidence of Adverse Events (AEs)

    Characterized by severity and seriousness of AEs, laboratory abnormalities and other safety parameters such as electrocardiogram (ECG) changes

    Measured: From first dose until 30 days after the last dose intake

Secondary outcomes (8)

  1. Plasma concentration of S 55746

    Measured: 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

  2. The pharmacokinetic (PK) profile of S 55746: Area Under the Curve [AUC]

    Measured: 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

  3. The PK profile of S 55746: Maximal Concentration [Cmax]

    Measured: 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

  4. Apoptotic activity from blood samples

    Measured: At Cycle 1(21 days)

  5. Objective Response Rate (ORR)

    Measured: Up to study completion (maximum of 3 years)

  6. Clinical Benefit Rate (CBR)

    Measured: Up to study completion (maximum of 3 years)

  7. Duration of response

    Measured: Up to study completion (maximum of 3 years)

  8. Progression Free Survival (PFS)

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2016 (estimated)
  2. Study startMar 2014
  3. Primary completion22 Oct 2018
  4. Study completion22 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02920697
Sponsor's protocol ID
CL1-55746-001
Other IDs
2013-003779-36, ISRCTN04804337
Status last verified
Jul 2024
First submitted
23 Aug 2016
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: 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.

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing S 55746 in people with Chronic Lymphocytic Leukaemia (CLL) and B-Cell Non-Hodgkin Lymphoma (NHL), run by Institut de Recherches Internationales Servier at 18 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France, Germany, Hungary, Poland, Singapore and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: During cycle 1 (21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02920697, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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