Etude : REACH-4 / CINC424F12201



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : REACH-4

Nom : CINC424F12201

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 25/11/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase I/II Open-label, Single-arm, Multi-center Study of Ruxolitinib Added to Corticosteroids in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease After Allogeneic Hematopoietic 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 : The study is an open-label, single-arm, Phase I/II multi-center study to investigate the PK, activity and safety of ruxolitinib added to the patient's immunosuppressive regimen in infants, children, and adolescents ages ≥28 days to <18 years old with either grade II-IV aGvHD or grade II-IV SR-aGvHD. This trial will utilize age groups: Group 1 includes patients ≥12y to <18y, Group 2 includes patients ≥6y to <12y, Group 3 includes patients ≥2y to <6y, and Group 4 includes patients ≥28days to <2y.

Study arm:
Experimental: Ruxolitinib
All patients will receive ruxolitinib in addition to corticosteroids +/-calcineurin inhibitor (CNI)

Current primary outcome:
Phase I:
- Measurement of pharmacokinetic (PK) parameter, AUC, in aGvHD and SR-aGvHD patients [ Time Frame: 28 days ]
- Measurement of PK parameter, Cmax, in aGvHD and SR-aGvHD patients [ Time Frame: 28 days ]
- Measurement of PK parameter, T1/2, in aGvHD and SR-aGvHD patients [ Time Frame: 28 days ]
- Measurement of PK parameter, Ctrough, in aGvHD and SR-aGvHD patients [ Time Frame: 28 days ]
- Age-based determination of RP2D for each of the groups 2-4 [ Time Frame: 28 days ]

Phase II:
- Overall response rate (ORR) [ Time Frame: 28 days ]

Current secondary outcomes:
- Percentage of all patients who achieve a CR or PR [ Time Frame: 56 Days ]
- Percentage of patients who achieved OR (CR+PR) [ Time Frame: To estimate ORR at Day 14. ]
- PK parameter: Area under the curve (AUC) versus safety [ Time Frame: 24 weeks ]
- Duration of response (DOR) [ Time Frame: 48 weeks ]
- Weekly cumulative steroid dose for each patient [ Time Frame: up to 56 days ]
- Overall Survival (OS) [ Time Frame: 2 years ]
- Event-Free Survival (EFS) [ Time Frame: 2 years ]
- Failure-Free Survival (FFS) [ Time Frame: 2 years ]
- Non Relapse Mortality (NRM) [ Time Frame: 2 years ]
- Incidence of Malignancy Relapse/Progression (MR) [ Time Frame: 2 years ]
- Incidence of cGvHD [ Time Frame: 2 years ]
- Monitoring of donor cell chimerism [ Time Frame: 2 years ]
- Questionnaire on acceptability and palatability [ Time Frame: 24 weeks ]
- Percentage of all patients who achieve a complete response (CR) or partial response (PR) [ Time Frame: 56 days ]
- PK parameter - maximum serum concentration (Cmax) versus efficacy [ Time Frame: 24 weeks ]
- PK parameter: Minimum serum concentration (Ctrough) versus safety [ Time Frame: 24 weeks ]
- PK parameter: Cmax versus safety [ Time Frame: 24 weeks ]
- PK parameter: Ctrough versus efficacy [ Time Frame: 24 weeks ]
- PK parameter: AUC versus efficacy [ Time Frame: 24 weeks ]
- PK parameter: AUC versus PD biomarkers [ Time Frame: 24 weeks ]
- PK parameter: Cmax versus PD biomarkers [ Time Frame: 24 weeks ]
- PK parameter: Ctrough versus PD biomarkers [ Time Frame: 24 weeks ]
- Percentage of patients who achieved Overall Response (OR) [ Time Frame: Up to 28 days and before start of additional aGvHD therapy ]

Phase : I/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 : - Male or female patients age ≥28 days and <18 years at the time of informed consent.
- Patients who have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of myeloablative or reduced intensity conditioning are eligible.
- Patients with a clinically confirmed diagnosis of grades II-IV aGvHD within 48 hours prior to study treatment start. Patients may have either: Treatment-naïve aGvHD (criteria per Harris et al. 2016) OR Steroid refractory aGvHD as per institutional criteria, and the patient is currently receiving systemic corticosteroids.
- Evident myeloid engraftment with ANC > 1,000/µl and platelet count >20,000/µl. (Use of growth factor supplementation and transfusion support is allowed.)

Other protocol-defined Inclusion/Exclusion may apply.

Critères de non-inclusion : - Has received the following systemic therapy for aGvHD: a) Treatment-naïve aGvHD patients have received any prior systemic treatment of aGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of acute GvHD. Patients are allowed to have received prior GvHD prophylaxis which is not counted as systemic treatment (as long as the prophylaxis was started prior to the diagnosis of aGvHD); OR b) SR-aGvHD patients have received two or more prior systemic treatments for aGvHD in addition to corticosteroids
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features (as defined by Jagasia et al 2015).
- Failed prior alloSCT within the past 6 months.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed, or who may require rapid immune suppression withdrawal of immune suppression as pre-emergent treatment of early malignancy relapse.
- Acute GvHD occurring after non-scheduled donor leukocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
- Any corticosteroid therapy for indications other than aGvHD at doses > 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of Screening. Routine corticosteroids administered during conditioning or cell infusion is allowed.
- Patients who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.

Other protocol-defined Inclusion/Exclusion may apply.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03491215
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 Bénédicte BRUNO

TEC / ARC / IDE :
Amandine GORALSKI
amandine.goralski@
chru-lille.fr
03.20.44.60.58

Ouverture de l'essai : OUVERT

MAJ : 25/11/2019