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Safety, Efficacy, and Assessment of Change in Spleen Volume Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet in Adult Participants With Relapsed / Refractory Myelofibrosis

Trial Status: Active

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, tolerability, 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 the study at approximately 23 countries worldwide. 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.

Inclusion Criteria

  • Must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days prior to randomization. --Has at least 2 symptoms with a score >= 3 or a total score of >= 12, as measured by the MFSAF v4.0.
  • Documented diagnosis of primary myelofibrosis (MF), post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF as defined by the World Health Organization (WHO) classification.
  • Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).
  • Must have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
  • Prior treatment with JAK2 inhibitor for >= 24 weeks that was stopped due to loss of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
  • Prior treatment with JAK2 inhibitor for < 24 weeks with documented disease progression while on JAK2 inhibitor 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 JAK2 inhibitor.
  • 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 JAK2 inhibitor.
  • A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of JAK2 inhibitor.
  • 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 JAK2 inhibitor.
  • Splenomegaly defined as spleen palpation measurement >= 5 cm below costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
  • Baseline platelet count >= 100 × 109/L.

Exclusion Criteria

  • Received prior treatment with a BH3-mimetic compound or prior use of > 1 JAK2 inhibitor.
  • Receiving medication that interferes with coagulation or platelet function except for low dose aspirin (up to 100 milligrams daily) and low molecular weight heparin (LMWH) within 3 days prior to the first dose of study drug or during the study treatment period.
  • Receiving anticancer therapy including chemotherapy, radiation therapy, hormonal therapy (with the exception of hormones for thyroid conditions or estrogen replacement therapy) within 30 days prior to first dose of study drug, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

South Carolina

Medical University of South Carolina

Trial Phase Phase III

Trial Type Treatment

Lead Organization

  • Primary ID M20-178
  • Secondary IDs NCI-2020-06012, 2020-000557-27
  • ID NCT04468984