 This is a randomized study medication assigned to participants by chance, multicenter more than one hospital, medical school team or medical clinic work on a medical research study study of 2 dosing regimens treatment arms of single-agent imetelstat in participants with intermediate-2 or high risk myelofibrosis MF whose disease is relapsed after or refractory to Janus Kinase JAK inhibitor treatment. Enrollment in the study may be approximately 160 participants if enrollment in Arm 1 is resumed after the second interim review. The study consists of 3 parts: Screening Phase 21 days before randomization; single-blind Treatment Phase from randomization until study drug discontinuation; and Follow up Phase until death, lost to follow-up, withdrawal of consent or study end, whichever occurs first. Participants in Arm 1 will receive imetelstat 9.4 milligram mgkilogram kg intravenously IV for every 3 weeks until disease progression, unacceptable toxicity, or study end and Arm 2 will receive imetelstat 4.7 mgkg IV for every 3 weeks until disease progression, unacceptable toxicity, or study end. Participants in Arm 2 may continue with their current imetelstat dose or have it increased to 9.4 mgkg at the investigators discretion. Percentage of spleen response and symptom response will be evaluated primarily. Participants safety will be monitored throughout the study. 