Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, as 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. The study has 2 arms - A and B. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. Adult participants with a diagnosis of relapsed/refractory (R/R) MF will be enrolled. Approximately 330 participants will be enrolled in approximately 210 sites across the world. In Arm A, participants will receive oral navitoclax tablet once daily with oral ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT as identified by the investigator. Treatment will continue until clinical benefit is not seen, 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.