Clinical Trial 21415

• Overview

  Study Title:

  An Open Label, Phase 1/1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination with Ruxolitinib in Patients with Myelofibrosis

  Objective:

  Primary * To identify the recommended Part 2 dose (RP2D) of imetelstat in combination with ruxolitinib * To evaluate the safety and preliminary clinical activity of RP2D of imetelstat in combination with ruxolitinib Secondary * Evaluate pharmacokinetics (PK) and immunogenicity of imetelstat and PK of ruxolitinib * Evaluate symptom response at Week 24 (Part 1 only) * Evaluate spleen response at Week 24a * Progression Free Survival (PFS) * Responses per 2013 IWG MRT criteria * Time to and duration of the response * Reduction of bone marrow fibrosis

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  Imetelstat (GRN163L); Jakafi (Ruxolitinib); Ruxolitinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Diagnosis of primary myelofibrosis (PMF) according to the revised World Health Organization (WHO) criteria or post-essential thrombocythemia-MF or post-polycythemia vera according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.
  • Dynamic International Prognostic Scoring System (DIPSS) intermediate-1, intermediate-2 or high-risk MF.
  • Candidate for ruxolitinib treatment: 1. Part 1 participants only: On ruxolitinib treatment for at least 12 weeks with at least 4 consecutive weeks immediately prior to enrollment at a stable dose. 2. Part 2 participants only: Candidate for ruxolitinib treatment as assessed by the investigator and has not previously been treated with a Janus kinase (JAK) inhibitor.
  • Clinical signs/symptoms of MF demonstrated by one of the following: 1. Measurable splenomegaly demonstrated by either a palpable spleen measuring greater than or equal to 5 cm below the left costal margin or a spleen volume greater than or equal to 450 cm^3 by MRI or CT. 2. Active symptoms of MF on the MFSAF v4.0.
  • Ineligible for or unwilling to undergo hematopoietic stem cell transplant at time of study entry.
  • Hematology laboratory test values within protocol defined limits.
  • Biochemical laboratory test values within protocol defined limits.
  • Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
  • Participants should follow protocol defined contraceptives procedures.
  • A woman of childbearing potential must have a negative serum or urine pregnancy test at screening.

• Exclusion Criteria

  Exclusion Criteria:
  • Peripheral blood blast count of greater than or equal to 10% or bone marrow blast count of greater than or equal to 10%.
  • Prior treatment with JAK inhibitor.
  • Known allergies, hypersensitivity, or intolerance to imetelstat or ruxolitinib or excipients.
  • Prior treatment with imetelstat.
  • Major surgery within 28 days prior to enrollment.
  • Any investigational drug regardless of class or mechanism of action, hydroxyurea, chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent less than or equal to 14 days prior to enrollment.
  • Prior history of hematopoietic stem cell transplant.
  • Prior history of partial or complete splenectomy.
  • Diagnosis or treatment for malignancy other than MF, except: Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before enrollment. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease.
  • Clinically significant cardiovascular disease.
  • Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection requiring IV antibiotics.
  • Active systemic hepatitis infection requiring treatment or any known acute or chronic liver disease unless related to MF. Carriers of hepatitis virus are permitted to enter the study.

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