Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis

Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.

TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0. Participants complete a symptom diary and rate the following seven MF symptoms: fatigue, night sweats, abdominal discomfort, pruritus, pain under the ribs on the left side, early satiety, and bone pain daily using a scale from 0 (absent) to 10 (worst imaginable), and the scores are averaged over 7 days, with a minimum of 4 days required to calculate the average score. Participants for whom a valid average score cannot be calculated either at baseline or post-baseline are considered non-responders. The TSS reflects the sum of the scores of these symptoms, for a maximum possible score of 70 (i.e., most severe symptom experience). Negative changes from Baseline indicate improvement.

Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.

Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of the first assessment where the spleen volume is less than 35% reduction from Baseline and is at least 25% increase from the nadir (the lowest spleen volume), confirmed relapse, or leukemic transformation per International Working Group (IWG) criteria, whichever is earlier.

The PROMIS Fatigue SF 7a is a 7-item patient-reported outcome measure that assesses the impact and experience of participants with fatigue over the past 7 days. Each item is scored on a 5-point Likert scale (1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always). Raw scores range from 7 to 35 and are subsequently transformed into a standardized T-score using the PROMIS wave 1 calibration (where a score of 50 represents the U.S. general population mean with a standard deviation of 10). Higher T-scores indicate greater fatigue severity. A decrease in T-score from Baseline represents a clinical improvement in fatigue symptoms.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from Baseline indicate improvement.

For a participant who is transfusion independent (TI) at Baseline with hemoglobin value < 10 g/dL, anemia response is achieved if the post-Baseline hemoglobin level increases by ≥2 g/dL without receiving packed red blood cells (PRBC) transfusion (for any reason) within 2 weeks and without any erythropoietin or mimetics within the last 4 weeks prior to the increase in hemoglobin level by ≥2g/dL was observed. Hemoglobin values more than 30 days after the last dose of study treatment or after the start of post-study treatment or disease progression, whichever is earlier, will not be considered in the analysis of anemia response.

For a participant who is transfusion dependent (TD) at Baseline, anemia response is defined as a period of at least 12 consecutive weeks without PRBC transfusion at any time after the first dose of study drug and on or prior to 30 days post last dose of study drug, the start of post-study treatment, disease progression or death, whichever occurs earlier.

OS is defined as the time from the date of randomization to the date of death from any cause.

Leukemia-free survival is defined as the number of days from the date of randomization to the onset date of documented leukemia, disease progression due to leukemia, or death due to leukemia, whichever occurs first.

Change in grade of bone marrow fibrosis was measured per the European consensus grading system through bone marrow biopsy. The percentage of participants who achieved reduction of at least 1 grade in bone marrow fibrosis compared to Baseline is reported.