Details

Details

Title A Phase 3, Randomized Study To Evaluate the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects with Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis who were Treated with Ruxolitinib

IRB GSI3Z14

CC 15-048

Hospital Main Campus

Phase Phase 3

Disease Myelofibrosis

Drug Momelotinib

Description

Description

Primary Objective
  • To determine the efficacy of MMB versus BAT in anemic or thrombocytopenic subjects with PMF or Post-PV/ET MF who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).
Secondary Objectives
  • To determine the effect of MMB compared with BAT on the improvement of total symptom score at Week 24
  • To determine the effect of MMB compared with BAT on rate of RBC transfusions through Week 24
  • To determine the effect of MMB compared with BAT on RBC transfusion independence rate at Week 24
  • To determine the effect of MMB compared with BAT on RBC transfusion dependence rate at Week 24
Inclusion Criteria

Inclusion Criteria

  1. Age ≥ 18 years old
  2. Palpable splenomegaly at least 5 cm below left costal margin
  3. Confirmed diagnosis of PMF in accordance with the WHO criteria, or Post-PV/ET MF in accordance with the IWG-MRT criteria (Appendix 3)
  4. Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by
    • Requirement for RBC transfusion while on ruxolitinib treatment, OR
    • Dose adjustment of ruxolitinib to < 20 mg twice-daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:
      • ≥ CTCAE Grade 3 thrombocytopenia, OR
      • ≥ CTCAE Grade 3 anemia, OR
      • ≥ CTCAE Grade 3 hematoma (bleed)
  5. High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS) (Appendix 6), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
  6. If receiving myelofibrosis therapy, must be on a stable dose of the same regimen for at least 2 weeks prior to screen date and through the screening period
  7. If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
  8. Acceptable laboratory assessments obtained within 14 days prior to Randomization
    • ANC ≥ 0.75 x 109/L in the absence of growth factor in the prior 7 days
    • Peripheral blood blast count < 10%
    • AST/SGOT and ALT/SGPT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
    • Calculated creatinine clearance of ≥ 45 mL/min
    • Direct bilirubin ≤ 2.0 x ULN
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  10. Life expectancy > 24 weeks
  11. Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years post-menopausal)
  12. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 5
  13. Females who are nursing must agree to discontinue nursing before the first dose of MMB
  14. Able to understand and willing to sign ICF
Exclusion Criteria

Exclusion Criteria

  1. Prior splenectomy
  2. Splenic irradiation within 3 months prior to randomization
  3. Use of investigational agent within 28 days prior to randomization
  4. Prior treatment with MMB
  5. Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to randomization
  6. Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (subjects receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the study); active or chronic bleeding event within 4 weeks prior to Randomization; symptomatic congestive heart failure (CHF) ; unstable angina pectoris; uncontrolled cardiac arrhythmia; or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
  7. QTc interval > 450 msec, unless attributed to bundle branch block
  8. History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission , or any other cancer that has been in complete remission for ≥ 5 years
  9. Known positive status for human immunodeficiency virus (HIV)
  10. Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
  11. Unresolved non-hematologic toxicities from prior therapies that are > CTCAE Grade 1 12) Use of strong CYP3A4 inducers within 1 week prior to Randomization
  12. Changes to dose of iron chelator therapy within 14 days prior to Randomization
  13. Presence of peripheral neuropathy ≥ CTCAE Grade 2
  14. Unwilling or unable to undergo a MRI or CT Scan per requirements in Section 6.2.10.2
  15. Known hypersensitivity to the study investigational medicinal products, the metabolites, or formulation excipients