Etude : TRANSFORM-1 / M16-191

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
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : TRANSFORM-1 / M16-191

Situation thérapeutique : Induction

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 29/11/2021
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase III randomisée, en double aveugle, contrôlée par placebo sur le navitoclax associé au ruxolitinib versus ruxolitinib chez des patients atteints de myélofibrose (TRANSFORM-1)

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Informations complémentaires
Schéma : Myelofibrosis is a type of bone marrow cancer that usually develops slowly and disrupts body's normal production of blood cells. It causes bone marrow scarring, leading to severe anemia that can cause weakness and fatigue. It can also cause a low number of blood-clotting cells called platelets, which increases risk of bleeding. Myelofibrosis often causes an enlarged spleen. The purpose of this study is to see if a combination of navitoclax and ruxolitinib is more effective and safe in assessment of change in spleen volume when compared to ruxolitinib in participants with myelofibrosis.

Navitoclax is an investigational drug for the treatment of myelofibrosis. Participants in this study are divided into two groups, called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of myelofibrosis will be enrolled. Around 230 participants will be enrolled in approximately 190 sites worldwide.

Participants will receive oral navitoclax tablet with oral ruxolitinib tablet or oral ruxolitinib tablet with oral placebo (no active drug) tablet and treatment may continue till the participant cannot tolerate the study drug, or benefit is not achieved, or other reasons which qualify for discontinuation of the study drug.

There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, magnetic resonance imaging (MRI) or computed tomography (CT) scan, bone marrow tests, checking for side effects, and completing questionnaires.

Study arms:
- Experimental: Navitoclax + Ruxolitinib
- Active Comparator: Placebo for Navitoclax + Ruxolitinib

Main objective:
To evaluate the effect of navitoclax in combination with ruxolitinib on splenomegaly response when compared to ruxolitinib in subjects with myelofibrosis.

Secondary objectives:
• To evaluate the effect of navitoclax in combination with ruxolitinib on the onset, magnitude, and duration of disease response, including Total Symptom Score (TSS), effects on spleen, bone marrow fibrosis, and anemia.
• To evaluate the effect of navitoclax in combination with ruxolitinib on measures of health-related quality of life (HRQoL), including fatigue, and physical functioning.
• To evaluate the effect of navitoclax in combination with ruxolitinib on overall survival (OS) and leukemia-free survival.

Phase : III

Stade : NA

1 (hémato), Rechute, Réfractaire
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 : • Subject ≥ 18 years of age.
• Subject with a documented diagnosis of primary myelofibrosis (MF) or secondary MF (post polycythemia vera [PPV] -MF or post essential thrombocythemia [PET] – MF) as defined by the World Health Organization classification.
• Subject must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) on at least 4 out of 7 days prior to Day 1.
• Subject classified as intermediate-2 or high-risk MF as defined by the Dynamic International Prognostic Scoring System.
• Subject has splenomegaly defined as spleen palpation measurement ≥ 5 cm below costal margin or spleen volume ≥ 450 cm^3 as assessed centrally by MRI or CT scan.
• Subject has at least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 12, as measured by the MFSAF v4.0.
• Subject with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Critères de non-inclusion : • Subject must not have received prior treatment with a JAK-2 inhibitor.
• Subject must not have received prior treatment with a BH3-mimetic compound or bromodomain and extra-terminal motif (BET) inhibitor.
• Subject must not be eligible for stem cell transplantation at time of study entry.
• Subject must not receive medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier de Roubaix - 11 Boulevard Lacordaire - 59100 ROUBAIX

Investigateur :
Docteur Mathieu WEMEAU

+33 3 20 99 31 31 | DECT 17959

Statut de l'essai : OUVERT

MAJ : 02/08/2021