A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Navitoclax In Combination With Ruxolitinib Versus Ruxolitinib In Subjects With Myelofibrosis (TRANSFORM-1)
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Navitoclax In Combination With Ruxolitinib Versus Ruxolitinib In Subjects With Myelofibrosis (TRANSFORM-1)
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 untill 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.
Inclusion Criteria:
Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health Organization (WHO) classification or Secondary MF (post polycythemia vera [PPV] - MF or Post Essential Thrombocythemia [PET] - MF) .
Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days immediately preceding the date of randomization.
-- Must have at least 2 symptoms with a score >=3 or a total score of >=12, as measured by the MFSAF v4.0.
Classified as intermediate-2, or high-Risk MF as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
Has splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below costal margin or spleen volume greater than or equal to 450 cubic cm as assessed centrally by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
Ineligible for stem cell transplantation at time of study entry due to age, comorbidities, or unfit for unrelated or unmatched donor transplant and other criteria per National Comprehensive Cancer Network guidelines.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Exclusion Criteria:
East Albury, New South Wales 2640, Australia
Yvoir, Namur 5530, Belgium
Sofiya, Sofia 1431, Bulgaria
Chambéry, Savoie 73007, France
Athens, 10676, Greece
Bologna, Emilia-Romagna 40138, Italy
Rome, Roma 00168, Italy
Nagoya, Aichi-ken 453-8511, Japan
Kashiwa-shi, Chiba 277-8577, Japan
Toon-shi, Ehime 791-0295, Japan
Ogaki-shi, Gifu 503-8502, Japan
Hitachi-shi, Ibaraki 317-0077, Japan
Kanoya-shi, Kagoshima-ken 893-0024, Japan
Kurashiki-shi, Okayama-ken 701-0192, Japan
Kurashiki-shi, Okayama-ken 710-8602, Japan
Hirakata-shi, Osaka 573-1191, Japan
Osakasayama-shi, Osaka 589-8511, Japan
Suita-shi, Osaka 565-0871, Japan
Izunokuni-shi, Shizuoka 410-2295, Japan
Bunkyo-ku, Tokyo 113-8431, Japan
Bunkyo-ku, Tokyo 113-8602, Japan
Chuo-shi, Yamanashi 409-3821, Japan
Petrozavodsk, Murmansk Oblast 185019, Russia
Saint Petersburg, 191024, Russia
Busan, Busan Gwang Yeogsi 47392, South Korea
Daegu, Daegu Gwang Yeogsi 41944, South Korea
Seongnam, Gyeonggido 13620, South Korea
Seoul, Seoul Teugbyeolsi 06591, South Korea
Santiago de Compostela, A Coruna 15706, Spain
Gothenburg, Västra Götaland County 413 45, Sweden
Taipei City, Taipei 100, Taiwan
Edirne, Istanbul, 22030, Turkey (Türkiye)
Kharkiv, Kharkiv Oblast 61070, Ukraine
Kyiv, 02091, Ukraine
Lviv, 79044, Ukraine
Oxford, Oxfordshire OX3 9DU, United Kingdom