Etude : CL1-65487-002 /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : CL1-65487-002

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 24/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapse or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C92 - Leucémie myéloïde

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C90 - Myélome multiple et tumeurs malignes à plasmocytes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM).

This study is designed in two parts:
- one part for dose escalation,
- one part for dose expansion.
The dose escalation part will be followed by expansion part at the MTD(s)/RP2D(s).
This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s) for S65487 in the indications.

Current primary outcome:
- Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: until the end of the first cycle (each cycle is 21days) ]
- Safety criterion
- Incidence and severity of Adverse Events [ Time Frame: through study completion an average of 6 months ]
- Safety and tolerability criteria
- Incidence and severity of Serious Adverse Events [ Time Frame: through study completion an average of 6 months ]
- Safety and tolerability criteria
- Number of participants with dose reductions [ Time Frame: through study completion an average of 6 months ]
- Number of participants with dose interruptions [ Time Frame: through study completion an average of 6 months ]
- Dose intensity [ Time Frame: through study completion an average of 6 months ]

Current secondary outcomes:
- The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC) [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]
- PK profile of S65487: Volume of distribution at steady-state (Vss) [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]
- PK profile of S65487: total CLearance (CL) [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]
- PK profile of S65487: terminal half-life (t½z) [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]
- Best Overall Response (BOR) [ Time Frame: Through study completion, an average of 6 months ]
- Best Response observed during the treatment period
- Overall Response Rate (ORR) [ Time Frame: Through study completion, an average of 6 months ]
- Proportion of patients in whom a complete response (CR) or a partial response (PR)

Phase : I

Stade : NA

NA
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia with relapsed or refractory disease without established alternative therapy. Or patients with measurable confirmed Multiple Myeloma (IMWG) with relapsed or refractory disease who have previously received at least three lines of treatment and without established alternative therapy. Or patients with histologically and measurable confirmed Non Hodgkin Lymphoma defined as Diffuse Large B cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) with relapsed or refractory disease who have received at least two lines of therapy (including rituximab) and without established alternative therapy.
- ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
- For NHL and MM patients: haematological function (independent of any growth factor support) based on the last assessment performed before inclusion, defined as: absolute neutrophil count (ANC) ≥ 1 x 109/L, haemoglobin ≥ 8 g/dL, platelet count ≥ 50 x 109/L.
- For AML patients: circulating Blood White Cell count (WBC count) < 25 x 109/L (with or without use of hydroxycarbamide) based on the last assessment performed before inclusion.
- Adequate renal function based on the last assessment performed before inclusion, assessed as Glomerular Filtration Rate (GFR) using Modification of Diet in Renal Disease (MDRD) Formula.
- Adequate hepatic function based on the last assessment performed before inclusion.

Critères de non-inclusion : - Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- Participation in another interventional study at the same time or another interventional study requiring investigational treatment intake within 3 weeks or at least 5 half-lives (whichever is longer) prior to the first S65487 administration.
- Participant already enrolled in the study (informed consent signed) and has received at least one dose of S65487.
- Patients who have not recovered from toxicity of previous anticancer therapy, including grade ≥ 2 non-hematologic toxicity, prior to the first IMP administration (including peripheral neurotoxicity). Certain toxicities will not be considered in this category (e.g. alopecia).
- Patients refractory to a previous treatment with a Bcl-2 inhibitor.
- For AML patients : Allogenic stem cell transplant within 3 months before the first IMP administration and/or patients who still receive immunosuppressive treatment and/or patients with active Graft-versus-host disease.
- For NHL and MM patients Prior allogenic stem cell transplant before the first IMP administration and/or Autologous stem cell transplant within 3 months before the first IMP administration.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03755154
Promoteur :
SERVIER (Institut de Recherches Internationales Servier)
Type de sponsor : Industriel
SERVIER (Institut de Recherches Internationales Servier)
92150 SURESNES

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 24/09/2019