Etude : REACH2 / CINC424C2301



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 : REACH2

Nom : CINC424C2301

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 06/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase III Randomized Open-label Multi-center Study of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation

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 : To evaluate the safety and efficacy of ruxolitinib compared to Best Available Therapy in patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation

Study arms:
- Active Comparator: Ruxolitinib
Ruxolitinib 10 mg Bis In Diem (BID)
Intervention: Drug: Ruxolitinib
- Active Comparator: Best Available Therapy (BAT)
As selected by the investigator
Intervention: Drug: Best Available Therapy (BAT)

Current primary outcome:
Overall Response Rate (ORR) [ Time Frame: 28 Days ]

Current secondary outcomes:
- Durable Overall Response Rate [ Time Frame: Day 56 ]
- ORR [ Time Frame: Day 14 ]
- Duration of response (DOR) [ Time Frame: Up to 24 months ]
- Cumulative steroid dose [ Time Frame: 56 Days ]
- Overall Survival (OS) [ Time Frame: Up to 24 months ]
- Event-free survival [ Time Frame: Up to 24 months ]
- Failure-Free survival (FFS) [ Time Frame: Up to 24 months ]
- Non Relapse Mortality (NRM) [ Time Frame: Up to 24 months ]
- Malignancy Relapse/Progression (MR) [ Time Frame: Up to 24 months ]
- Incidence of chronic Graft versus Host Disease (cGvHD) [ Time Frame: Up to 24 months ]
- Pharmacokinetic (PK) parameter: Plasma concentration at peak (CMax) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
- Exposure-efficacy relationship of ruxolitinib in corticosteroid refractory aGvHD [ Time Frame: 168 Days ]
- Patient Reported Outcomes (PROs): Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) [ Time Frame: Baseline, Up to 30 day follow-up visit ]
- Patient Reported Outcomes (PROs): EuroQol-5D-5L change [ Time Frame: Baseline, Up to 30 day follow-up visit ]
- Pharmacokinetic (PK) parameter: Area Under the Curve (AUC) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
- Pharmacokinetic (PK) parameter: total body clearance of ruxolitinib from the plasma after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
- Pharmacokinetic (PK) parameter: apparent volume of distribution during terminal phase after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
- Best Overall Response (BOR) [ Time Frame: up to day 28 ]
- Pharmacokinetic (PK) parameter: Ctough [ Time Frame: 168 Days ]

Phase : III

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 : - Have undergone Allogeneic Stem Cell Transplanttaion (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
-Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
- Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
* Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR
* Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR
* Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
- Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR
- Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days.

Other protocol-defined inclusion/exclusion criteria may apply.

Critères de non-inclusion : - Has received more than one systemic treatment for steroid refractory aGvHD.
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus (HCV) based on assessment by the treating physician.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.

Other protocol-defined inclusion/exclusion criteria may apply.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02913261
Promoteur :
Novartis Pharmaceuticals
Type de sponsor : Industriel
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 Valérie Coiteux

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

Ouverture de l'essai : CLOS

MAJ : 06/09/2019