TRANSFORM-2: This phase III trial is comparing the effectiveness of two treatments (chemotherapy + immunotherapy, versus the best available therapy) in myelofibrosis patients who have got worse or not responded to previous treatmentA 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

Inclusion

• 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:

    • Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
    • A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
    • A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
    • A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
  • 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.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
• Baseline platelet count >= 100 × 10^9/L.