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

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. The main 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 (mg)/kilogram (kg) intravenously (IV) for every 3 weeks until
disease progression, unacceptable toxicity, or study end and Arm 2 will receive imetelstat
4.7 mg/kg 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 mg/kg at the investigator's discretion. Percentage of spleen response and
symptom response will be evaluated primarily. Participants' safety will be monitored
throughout the study. The study is closed to further participant enrollment. Participants
benefiting from study treatment will continue to receive imetelstat in Extension Phase for
approximately 2 years or until loss of benefit or unacceptable toxicity. Participants
entering to Extension phase from Follow up Phase will continue follow up for safety via
serious adverse event collection and for survival status. The Extension Phase will end
approximately 2 years after the clinical cutoff for the final analysis of the main study, or
when the sponsor terminates the study, whichever occurs first.

Inclusion Criteria:

- Diagnosis of PMF according to the revised WHO criteria; or PET-MF or PPV-MF according
to the IWG-MRT criteria

- DIPSS intermediate-2 or high risk MF

- Measurable splenomegaly prior to study entry as demonstrated by palpable spleen
measuring greater than or equal to (>=) 5 cm below the left costal margin OR spleen
volume of >= 450 cm^3 measured by MRI

- Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0
to10 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 JAK inhibitor therapy

- 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

- 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