A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis

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: * Part 1 participants: On ruxolitinib treatment for at least 12 weeks with at least 4 consecutive weeks immediately prior to enrollment at a stable dose. * Part 2 participants: Candidate for ruxolitinib treatment as assessed by the investigator and has not previously been treated with a JAK inhibitor (Cohort A) OR currently receiving ruxolitinib per standard of care for at least 12 weeks with at least 4 consecutive weeks at a stable dose prior to enrollment (Cohort B). Note that the study will no longer recruit participants into Cohort A. * Active symptoms of MF on the MFSAF v4.0 demonstrated by: * Part 1 participants only: At least 2 symptoms with a score ≥ 1 * Part 2 participants only: At least 2 symptoms with a score of ≥ 3, or a total score of at least 10. * 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: * Peripheral blood blast count of ≥10% or bone marrow blast count of ≥10%. * Prior treatment with JAK inhibitor (except for participants being dosed optimized on ruxolitinib treatment prior to screening and enrollment in part 1 or Part 2 Cohort B). * 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, (except for ruxolitinib for participants being dose optimized prior to enrollment), immunomodulatory or immunosuppressive therapy, corticosteroids \>30 mg/day prednisone or equivalent ≤14 days prior to enrollment. * Prior history of hematopoietic stem cell transplant. * Diagnosis or treatment for malignancy other than MF, except: * Malignancy treated with curative intent and with no known active disease present for ≥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.