Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2), Incorporating Extension Arm C - Continued Access for Navitoclax to Roll Over Subjects From Studies M10-166, M16-109, M16-191, and M19-753
Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2), Incorporating Extension Arm C - Continued Access for Navitoclax to Roll Over Subjects From Studies M10-166, M16-109, M16-191, and M19-753
Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, compared to best available therapy, for adult participants with MF.
Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. Participants in this study will be randomly selected (like picking numbers out of a hat) to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to pick which treatment arm a participants enters. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. In Arm C, participants will receive navitoclax. Adult participants with a diagnosis of MF that came back or did not get better after earlier treatment will be enrolled. Approximately 330 participants will be enrolled in approximately 322 sites across the world.
In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the investigator. In Arm C, participants will receive navitoclax tablet by mouth once daily. Participants will receive the study drug until they experience no benefit (determined by the investigator), participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
Inclusion Criteria:
Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window.
-- Has at least 2 symptoms each with an average score >= 3 or an average total score of >= 12, as measured by the MFSAF v4.0.
Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3.
Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:
Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.
Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity.
Exclusion Criteria:
Grand Junction, Colorado 81501-6132, United States
Elk Grove Village, Illinois 60007-3361, United States
New Orleans, Louisiana 70121, United States
Greenvale, New York 11548-1219, United States
New York, New York 10016-6028, United States
New York, New York 10065-6007, United States
Winston-Salem, North Carolina 27157-0001, United States
Gettysburg, Pennsylvania 17325, United States
Philadelphia, Pennsylvania 19104-4238, United States
San Antonio, Texas 78229, United States
East Albury, New South Wales 2640, Australia
Sofiya, Sofia 1431, Bulgaria
Toronto, Ontario M5G 2M9, Canada
Lévis, Quebec G6V 3Z1, Canada
Chambéry, Savoie 73007, France
Bochum, North Rhine-Westphalia 44791, Germany
Athens, 10676, Greece
RION Patras Achaia, 26504, Greece
Nyíregyháza, Szabolcs-Szatmár-Bereg 4400, Hungary
Bologna, Emilia-Romagna 40138, Italy
Rome, Lazio 00168, Italy
Monza, Monza E Brianza 20052, Italy
Turin, Piedmont 10126, Italy
Reggio Calabria, 89125, Italy
Nagoya, Aichi-ken 453-8511, Japan
Kashiwa-shi, Chiba 277-8577, Japan
Toon-shi, Ehime 791-0295, Japan
Shiwa-gun, Iwate 028-3695, Japan
Kamakura-shi, Kanagawa 247-8533, Japan
Kurashiki-shi, Okayama-ken 710-8602, Japan
Hirakata-shi, Osaka 573-1191, 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
Shinjuku-ku, Tokyo 160-0023, Japan
Sumida-ku, Tokyo 130-8575, Japan
Chuo-shi, Yamanashi 409-3821, Japan
Tokyo, 108-8639, Japan
Poznan, Greater Poland Voivodeship 60-569, Poland
Lublin, Lublin Voivodeship 20-081, Poland
Lodz, Łódź Voivodeship 93-513, Poland
Saint Petersburg, 191024, Russia
Seoul, Seoul Teugbyeolsi 06591, South Korea
Santiago de Compostela, A Coruna 15706, Spain
Taipei City, Taipei 100, Taiwan
Edirne, Istanbul, 22030, Turkey (Türkiye)
London, Greater London SE1 9RT, United Kingdom
Great Yarmouth, Norfolk NR31 6LA, United Kingdom