Etude : KRT-232-102 /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : KRT-232-102

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 03/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

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 phlebotomy-dependent polycythemia vera (PV). Inhibition of MDM2 in PV is a new mechanism of action in PV. In Part A, patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon. In Part B, patients must be resistant or intolerant to hydroxyurea.

This study is a global, open-label Phase 2a/2b study to determine the efficacy and safety of KRT-232. In Part A of the study, patients will be randomly assigned to 3 arms with 2 different doses and 2 different dosing schedules of KRT 232. In Part B of the study, patients will be randomized either to treatment with KRT-232 administered at the recommended dose and schedule from Part A or to treatment with ruxolitinib.

Study arms:
- Experimental: Part A Arm 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 Arm 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 Arm 3
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Intervention: Drug: KRT-232
- Experimental: Part B KRT-232 Arm
Recommended KRT-232 dose and schedule from Part A
Intervention: Drug: KRT-232
- Active Comparator: Part B Ruxolitinib Arm
Ruxolitinib per approved prescribing label
Intervention: Drug: Ruxolitinib

Current primary outcome:
Proportion of patients with splenomegaly achieving a response at Week 32 [ Time Frame: 32 weeks ]
Response defined as having achieved both of the following:
* The absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32, with no more than one phlebotomy eligibility occurring post-randomization and prior to the Week 8 visit
* A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 32

Current secondary outcomes:
- Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) [ Time Frame: 4 years ]
- Duration of response after achieving phlebotomy independence [ Time Frame: 4 years ]
- Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome [ Time Frame: 32 weeks ]
- Change from baseline of EORTC-QLQ-C30 patient-reported outcome [ Time Frame: 32 weeks ]

Phase : II

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 : - Confirmed diagnosis of PV (WHO 2016)
- ECOG ≤ 2
- Part A: patients with and without splenomegaly are eligible
- Part A: patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon
- Part B: only patients with splenomegaly are eligible
- Part B: patients must be resistant or intolerant to hydroxyurea

Critères de non-inclusion : - Diagnosis of post-PV myelofibrosis (IWG-MRT)
- Prior treatment with MDM2 inhibitors, p53-directed therapies, HDAC, BCL 2 inhibitors
- Splenic irradiation within 3 months prior to the first dose of study treatment
- Clinically significant thrombosis within 3 months of screening
- Grade 2 or higher QTc prolongation
- Part B: prior treatment with a JAK inhibitor
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03669965
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