Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor
Condition: Myelofibrosis
MeSH terms: Primary Myelofibrosis
Intervention: Imetelstat 4.7 mg/kg; Imetelstat 9.4 mg/kg
Intervention description: Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle. Study drug was administered intravenously until disease progression, unacceptable toxicity, or study end.; Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end.
Intervention MeSH terms: Niacinamide; Imetelstat; Motesanib diphosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Masking description: Initially single-blind; treatments unmasked after 1st Interim Analysis and continued as open-label treatment.
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Imetelstat; GRN163L; Relapsed/refractory to JAKi; IMbark

Summary:

      The purpose of this study is to evaluate the efficacy and safety of 2 dose regimens of
      imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) whose disease
      is relapsed after or is refractory to Janus Kinase (JAK) inhibitor treatment. Key secondary
      endpoint includes overall survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of primary myelofibrosis (PMF) according to the revised WHO criteria; or
             post-essential thrombocythemia-myelofibrosis (PET-MF) or post-polycythemia
             vera-myelofibrosis (PPV-MF) according to the International Working
             Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

          -  Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or highrisk MF.

          -  Measurable splenomegaly prior to study entry as demonstrated by palpable spleen
             measuring ≥ 5 cm below the left costal margin OR spleen volume of ≥ 450 cm^3 measured
             by magnetic resonance imaging (MRI).

          -  Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0
             to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2
             of the symptoms.

          -  Documented progressive disease during or after Janus kinase (JAK) inhibitor therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

        Exclusion Criteria:

          -  Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.

          -  Prior treatment with imetelstat.

          -  Any chemotherapy or MF-directed therapy, investigational drug, hydroxyurea,
             immunomodulatory or immunosuppressive therapy, corticosteroids or JAK inhibitor
             therapy ≤14 days prior to randomization.

          -  Major surgery within 4 weeks prior to randomization.

          -  Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus
             are permitted to enter the study), of any type or known acute or chronic liver disease
             including cirrhosis.

          -  Prior history of hematopoietic stem cell transplant.