Etude : KRT-232-101 /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : KRT-232-101

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 11/06/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post-ET-MF) Who Have Failed a JAK Inhibitor

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2 different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.

Study arms:
- Experimental: Part A Cohort 1
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Intervention: Drug: KRT-232

- Experimental: Part A Cohort 2
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
Intervention: Drug: KRT-232

- Experimental: Part A Cohort 3
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Intervention: Drug: KRT-232

- Experimental: Part B
Recommended KRT-232 dose and schedule from Part A
Intervention: Drug: KRT-232

Current primary outcome:
To determine spleen response [ Time Frame: 24 weeks ]. The proportion of patients achieving a ≥ 35% spleen volume reduction from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan

Current secondary outcomes:
- To determine the change in modified MPN-SAF Total Symptom Score (TSS) at Week 24 and Week 48 [ Time Frame: 48 weeks ]
Proportion of patients who have at least a 50% reduction from Baseline to Week 24 and Week 48 in the total symptom score as measured by the modified MPN-SAF v2.0
- RBC transfusion independence at Week 24 [ Time Frame: 24 weeks ]
Proportion of patients who have RBC transfusion independence at week 24
- Complete remission and partial remission defined according to International Working Group-Myeloproliferative Neoplasms Research and Treatment and modified European LeukemiaNet criteria [ Time Frame: 24 weeks ]
Proportion of patients who have complete remission and partial remission at week 24

Phase : II

Stade : NA

2, 3, 4, X
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
- High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
- Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
- ECOG ≤ 2

Critères de non-inclusion : - Prior splenectomy
- Splenic irradiation within 3 months prior to the first dose of KRT-232
- Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
- Prior MDM2 inhibitor therapy or p53-directed therapy
- Prior treatment with HDAC or BCL-2 inhibitors
- Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03662126
Promoteur :
KARTOS Therapeutics
Type de sponsor : Industriel
275 Shoreline Drive, Suite 100 Redwood City, CA 94065
00000 HORS FRANCE

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 :
Docteur Nathalie CAMBIER

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

Ouverture de l'essai : OUVERT

MAJ : 11/06/2019